Clinical-anatomical and biological forms
The histological picture of a tumor is closely related to its primary location. Central (root) cancer is distinguished, which forms from the epithelial lining of large bronchi—main, lobular, or segmental. Peripheral cancer originates in smaller structures: small bronchi, bronchioles, and alveoli. In late stages, when the neoplasm reaches giant sizes and its primary boundaries cannot be determined, it is referred to as massive cancer.
From a clinical and biological perspective, all histological variants are combined into two major categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). This division is critically important because these groups differ fundamentally in morphology, clinical course, response to chemotherapy, and overall prognosis.
Microscopic structure of tumors
The histological classification is based on histogenesis and the features of cellular tissue structure:
- Squamous cell carcinoma is divided by degree of differentiation (well-, moderately-, and poorly differentiated). The keratinizing subtype is characterized by the presence of keratohyalin granules, the formation of "cancer pearls," and rare mitoses. The non-keratinizing subtype consists of oval or polygonal cells with eosinophilic cytoplasm, pronounced nuclear polymorphism, and frequent (including atypical) mitoses.
- Small cell carcinoma is represented by classical (oat cell, lymphocyte-like, intermediate cell) and combined variants.
- Adenocarcinoma may have acinar, papillary, solid (with mucus production) structure; bronchioloalveolar carcinoma is also distinguished separately.
- Large cell carcinoma includes giant cell and clear cell variants.
- Carcinoid tumor belongs to neuroendocrine neoplasms, but is staged using the TNM system similarly to non-small cell lung cancer.
- Bronchial gland carcinoma includes mucoepidermoid, adenoid cystic, and other specific types.
Also, the classification distinguishes adenosquamous carcinoma.
Morphofunctional features and histogenesis
With standard hematoxylin and eosin staining, glandular structures are visualized in well-differentiated adenocarcinomas. However, light microscopy does not always provide an exhaustive picture. For example, large cell carcinoma at the light optical level appears as an accumulation of large cells without visible signs of differentiation. Only with the use of electron microscopy and histochemistry can features of glandular or squamous epithelium be detected in them.
A similar situation is observed in small cell carcinoma. Under a light microscope, these are small undifferentiated cells, but deeper examination reveals heterogeneous differentiation: squamous, glandular, and, most commonly, neuroendocrine. It is the predominance of neuroendocrine properties that explains the specifics of the clinical course of SCLC.
The histogenesis of peripheral cancer is complex. Its development involves basal, ciliated, and goblet cells of the bronchi and bronchioles, as well as type II pneumocytes and Clara cells. This causes a wide histological diversity of peripheral tumors, among which adenocarcinomas dominate, bronchioloalveolar carcinoma occurs, and small cell or squamous types are significantly less frequent.
Immunohistochemistry and tumor markers
For precise differential diagnosis of histological types and evaluation of treatment efficacy, specific tumor markers are used. For example, the immunoperoxidase method makes it possible to detect pancytokeratins in cells of highly differentiated keratinizing squamous cell carcinoma.
| Histological type | Specific markers |
|---|---|
| Small cell carcinoma | Neuron-specific enolase (NSE) |
| Squamous cell carcinoma | CYFRA 21-1, squamous cell carcinoma antigen (SCC) |
| Adenocarcinoma | CYFRA 21-1, cancer antigen 125 (CA-125) |
| Large cell carcinoma | CYFRA 21-1, SCC, carcinoembryonic antigen (CEA) |
To determine the stage of a confirmed tumor, the international TNM classification (9th edition, 2024) is used, evaluating the primary tumor (T), regional lymph node involvement (N), and the presence of distant metastases (M).
For quick memorization of tumor markers: cytokeratin 19 fragment (CYFRA 21-1) is found in all major types of non-small cell cancer, whereas neuron-specific enolase (NSE) is exclusively characteristic of small cell cancer.
Class and exam questions
How does keratinizing squamous cell carcinoma differ from non-keratinizing?
In the keratinizing variant, "cancer pearls," keratohyalin granules form, and mitoses are rare. The non-keratinizing type is characterized by nuclear polymorphism and frequent atypical mitoses.
Why is small cell carcinoma often accompanied by paraneoplastic syndromes?
During electron microscopic and histochemical examination, the predominance of neuroendocrine differentiation is revealed in the cells of this tumor.
Which cells give rise to peripheral lung cancer?
It develops from the epithelium of small bronchi and bronchioles (basal, goblet, ciliated cells), as well as with the participation of Clara cells and type II pneumocytes.
What else to study on this topic
- Detailed histogenesis of central lung cancer and its predominant histological types.
- Decoding of T1–T4, N0–N3, and M0–M1 gradations in the TNM classification (9th edition).
- Summary staging grouping of lung cancer into stages I–IV.
- Paraneoplastic syndromes in small cell lung cancer.
- Histology of squamous cell carcinoma of other localizations (for morphological comparison).
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