Bronchogenic Carcinoma

Overview

Bronchogenic Carcinomas are malignant neoplasms that arise from cells of the respiratory epithelium and account for over 95% of all primary lung tumors. Lung tumors are subdivided into two basic histological categories which display distinct clinical courses and are treated with different strategies. However, regardless of histological subtype the risk of all bronchogenic carcinomas profoundly increases with cigarette smoking. Below we discuss the subtypes, morphology, epidemiology, and clinical consequences of bronchogenic carcinomas.

Subtypes

Four basic histological subtypes of bronchogenic carcinoma have been defined and include small cell carcinoma, large cell carcinoma, squamous cell carcinoma, and adenocarcinoma (In some cases tumors of mixed histological subtype exist). From a clinical perspective, only histological differentiation of the small cell subtype from the others is of any benefit as these two groupings displays distinct clinical courses and treatment modalities.
In general, Small Cell Lung Cancers (SCLCs) have etastasized]] at the time of diagnosis; consequently, only chemotherapy and radiotherapy are used for treatment with the expectation that disease will ultimately relapse. Non-Small Cell Lung Cancers (NSCLCs) refer to any of the other non-small cell histological subtypes of bronchogenic carcinoma. NSCLCs are often still localized to the lung at diagnosis and thus surgical resection is used for treatment. Although surgery is combined with chemo- and radiotherapy, NSCLCs appear to be less sensitive to chemotherapeutics and radiation. Consequently, the clinical distinction between SCLCs and NSCLCs is primarily for purposes of determining whether a surgical approach should be attempted.

Morphology

As discussed above, four basic histological subtypes of bronchogenic carcinoma exist. In reality, histological differentiation between the small cell and non-small cell grouping of subtypes is most important. However, we also list some basic morphological features of the NSCLC subtypes for purposes of completeness.

SCLCs tend to grow centrally in the lung and appear as sheets of cells with scant cytoplasm, hyperchromatic nuclei, and indistinct nucleoli. The tumors are thought to arise from neuroendocrine cells of the respiratory epithelium and thus neoplastic cells can often produce a variety of peptide hormones that may result in paraneoplastic syndromes.

In general, NSCLCs are distinguished from SCLCs by their much more abundant cytoplasm, prominent nucleoli, and their tendency to grow in a glandular or squamous architecture. The squamous cell subtype is a bona fide squamous cell carcinoma that is thought to arise from squamous metaplasia of the respiratory epithelium in response to chronic cigarette smoke irritation. These tumors tend to arise centrally, near the hilum, and although some tumors may display highly undifferentiated cells, well-differentiated areas may exist that develop keratin pearls. Adenocarcinomas tend to arise peripherally and are thought to develop from atypical, mucin-producing clara cells. Bronchial-derived adenocarcinomas grow in a variety of architectures, including glandular and solid forms, whereas bronchioloalveolar adenocarcinomas characteristically grow in as a single-cell layer along the architecture of pre-existing alveoli. large cell carcinomas tend to arise peripherally and likely represent undifferentiated and highly anaplastic derivatives of squamous cell carinomas or adenocarcinomas.

Epidemiology

Bronchogenic carcinomas are sadly extremely common and extremely deadly, making them the most common cause of cancer death in both men and women. In the absence of the obvious risk factors detailed below, bronchogenic carcinomas are exceedingly rare, although it still possible and typically manifests as the adenocarcinoma subtype. Indeed, the incidence of lung cancers largely tracks patterns of smoking incidence by 20-30 years.

Smoking: Cigarette smoking is the most obvious risk factor for developing any subtype of bronchogenic carcinoma and the risk of cancer development rises progressively with each pack-year
Asbestos: Asbestos exposure is a major risk factor for bronchogenic carcinoma especially in combination with smoking likely because cigarette carcinogens can adsorb and become concentrated on asbestos fibers
Radiation Injury: A higher incidence of bronchogenic carcinoma has been observed in workers of the uranium and radium industries
Other Environmental Exposures: Exposure to nickel or chromates increases risk

Clinical Consequences

Lung cancers may present with a wide variety of symptomology that can arise from contiguous tumor growth within or adjacent to the lung, metastatic spread, or due to production of biologically active molecules. However, a small percentage of lung cancers are detected incidentally on chest radiography as solitary nodules.

Lung tumors can grow into bronchi, causing irritation and obstruction of the airway along with hemorrhage into the lumen. Clinically, this may manifest as a chronic cough, wheezing, dyspnea, hemoptysis, along with atelectasis downstream of airway obstruction.

Extension into the pleura and chest wall may cause chest pain while obstruction of the pleural lymphatics or direct involvement of the pleura may result in pleural effusions. Esophageal involvement may cause dysphagia. Pericardial involvement may result in pericardial effusions. Lung tumors may grow to place pressure on the recurrent laryngeal nerve, resulting in hoarseness. Growing tumors may place pressure on the superior vena cava, resulting in its obstruction and symptoms of superior vena cava syndrome.
Pancoast Tumors refer to apical lung tumors that extend into adjacent structures, especially local nerves. Pancoast tumors can derange the brachial plexus, resulting in shoulder pain, and plae pressure on afferent SNS fibers that travel above the lung apex and control ocular functions, resulting in "Horner's Syndrome" characterized by a triad of miosis, ptosis, and ipsilateral facial anhidrosis.

Given the enormous propensity, especially of SCLCs, to metastasize, patients may display a wide variety of symptoms associated metastatic foci of cancer. Virtually any organ can be seeded by lung cancers and thus the variety of symptomology can be diverse.

Lung tumors can secrete a wide variety of biologically active molecules which can result in a variety of paraneoplastic syndromes. For example, squamous cell NSCLCs may produce PTH or a PTH-like peptide that can result in hypercalcemia. Alternatively SCLCs can synthesize ADH, resulting in SIADH, or may secrete ACTH, which can yield hypokalemia or Cushing Syndrome.

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