Histology of Carcinoma

Features of peripheral cancer histogenesis

Peripheral carcinomas develop from the epithelial lining of small bronchi and bronchioles. Basal, goblet, and ciliated cells are involved in this process. However, the key feature of the histogenesis of this tumor type is the active participation of Clara cells and type II alveolar cells. It is this specific cellular composition that provides pronounced microscopic diversity compared to centrally located tumors. In the peripheral regions of the lung, glandular forms (various variants of adenocarcinoma) and bronchioloalveolar carcinoma are absolutely dominant. At the same time, squamous cell and small cell variants of carcinoma form extremely rarely here.

Squamous cell carcinoma

This type of tumor belongs to the group of non-small cell lung cancer (NSCLC). During immunohistochemical examination, pancytokeratins, the specific protein keratohyalin, and low-molecular-weight cytokeratins are reliably detected in the cytoplasm of tumor cells. The final morphological picture on the micropreparation directly depends on the degree of tissue maturity (differentiation):

• Well-differentiated carcinoma: cells retain pronounced stratification and clear intercellular bridges. The main diagnostic marker is the presence of extracellular keratinization, in which characteristic layered structures known as "cancer pearls" form in the tissue. The complexity of the tissue structure is fully preserved here.
• Moderately differentiated carcinoma: the keratinization process changes character and moves inside the cells (intracellular keratinization). The complexity of tissue architecture begins to break down, but the intercellular bridges and overall stratification of the layer are still clearly visible.
• Poorly differentiated carcinoma: histological signs of keratinization almost completely disappear. The tissue structure is severely distorted (pronounced disruption of complexity), although basic stratification and intercellular contacts are partially preserved.

Adenocarcinoma and large cell carcinoma

Adenocarcinoma (glandular cancer) is also included in the broad category of NSCLC. With standard hematoxylin and eosin staining of sections, well-differentiated forms demonstrate clearly formed glandular structures. Tumor cells in such carcinomas are capable of actively producing mucus and pulmonary surfactant, and immunohistochemistry confirms the presence of high-molecular-weight cytokeratins. Several structural variants of adenocarcinoma are distinguished: acinar, papillary, lepidic, solid (with obligatory mucus production), and papillary bronchioloalveolar.

Large cell carcinoma under routine light microscopy looks like a featureless cluster of large atypical cancer cells without any obvious signs of specialization. However, the use of more complex methods—electron microscopy or histochemistry—allows the detection of hidden ultrastructural features of glandular or squamous epithelium. Giant cell and clear cell variants of carcinoma are traditionally attributed to this type.

Small cell carcinoma and rare forms

Small cell carcinoma visually consists of very small, undifferentiated cells. Despite the apparent morphological simplicity under a conventional light microscope, finer research methods (electron microscopy) reveal the extremely diverse nature of these cells. Most commonly, neuroendocrine differentiation predominates in the tissue, but squamous, glandular, or entirely unclassifiable elements are also encountered. The classic variant of small cell carcinoma includes oat cell, lymphocyte-like, and intermediate cell types. A combined variant and poorly differentiated neuroendocrine carcinoma are also distinguished.

Among other, rarer histological forms, the classification distinguishes:

• Adenosquamous carcinoma (a tumor with a mixed adenosquamous structure).
• Carcinoid tumors (specifically, atypical carcinoid, representing a moderately differentiated neuroendocrine carcinoma).
• Bronchial gland cancer (includes mucoepidermoid and adenoid cystic carcinoma).

Laboratory diagnostics and tumor markers

To accurately verify the histological type of carcinoma in modern laboratory diagnostics, specific tumor markers are used. Their detection helps differentiate tumors with similar morphology:

Class and exam questions

What else to study on this topic

• Immunohistochemical profile of various carcinoma types
• Morphological differences between acinar and solid adenocarcinoma
• Electron microscopic picture of large cell carcinoma
• Structural features of carcinoid tumors
• Mechanisms of mucus and surfactant production in glandular cancer

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