Small cell lung cancer is a histological type of malignant lung tumor with an extremely aggressive course and a poor prognosis. Clinically manifested by cough, hemoptysis, shortness of breath, chest pain, weakness, weight loss; in the later stages – symptoms of mediastinal compression. Instrumental methods for the diagnosis of small cell lung cancer (radiography, CT, bronchoscopy, etc.) should be confirmed by the results of tumor or lymph node biopsy, cytological analysis of pleural exudate. Surgical treatment is advisable only in the early stages; the main role is assigned to polychemotherapy and radiation therapy.
Meaning
Small cell lung cancer is one of the intensively proliferating tumors with a high potential for malignancy. In pulmonology, disease is much less common (15-20%) than non-small cell lung cancer (80-85%), but it is characterized by rapid development, contamination of the entire lung tissue, earlier and extensive metastasis. In the vast majority of cases, disease develops in smoking patients, more often in men. The greatest incidence is recorded in the age group of 40-60 years. Almost always, the tumor begins to develop as a central lung cancer, but very soon it metastasizes to bronchopulmonary and mediastinal lymph nodes, as well as distant organs (skeletal bones, liver, brain). Without special antitumor treatment, the median survival is no more than 3 months.
Causes of small cell lung cancer
Tobacco smoking is considered to be the main and most significant cause of pathology, and the main aggravating factors are the patient’s age, the experience of nicotine addiction and the number of cigarettes smoked per day. Due to the increasing prevalence of addiction among women in recent years, there has been a tendency to increase the incidence of disease among the fairer sex.
Other potentially significant risk factors include: hereditary burden on oncopathology, unfavorable ecology in the region of residence, harmful working conditions (contact with arsenic, nickel, chromium). The background on which lung cancer most often occurs can be transferred tuberculosis of the respiratory system, chronic obstructive pulmonary disease (COPD).
The problem of histogenesis of small cell lung cancer is currently being considered from two positions – endodermal and neuroectodermal. Proponents of the first theory tend to the point of view that this type of tumor develops from the cells of the epithelial lining of the bronchi, which are similar in structure and biochemical properties to small cell cancer cells. Other researchers are of the opinion that the cells of the APUD system (diffuse neuroendocrine system) give rise to the development of small cell cancer. This hypothesis is confirmed by the presence of neurosecretory granules in tumor cells, as well as increased secretion of biologically active substances and hormones (serotonin, ACTH, vasopressin, somatostatin, calcitonin, etc.) in small cell lung cancer.
Classification
The staging of small cell carcinoma according to the international TNM system does not differ from that of other types of lung cancer. However, to date, a classification that distinguishes localized (limited) and widespread stages of disease is relevant in oncology. The limited stage is characterized by a unilateral tumor lesion with an increase in the basal, mediastinal and supraclavicular lymph nodes. With a common stage, there is a transition of the tumor to the other half of the chest, cancerous pleurisy, metastases. About 60% of the detected cases are in the common form (stage III–IV according to the TNM system).
Morphologically, oat cell carcinoma, cancer from intermediate type cells and mixed (combined) oat cell carcinoma are distinguished within small cell lung cancer. Ovarian cell carcinoma is microscopically represented by layers of small spindle-shaped cells (2 times larger than lymphocytes) with rounded or oval nuclei. Cancer from intermediate type cells is characterized by larger cells (3 times more lymphocytes) of rounded, oblong or polygonal shape; cell nuclei have a clear structure. The combined histotype of the tumor is said to be a combination of morphological signs of ovarian cell carcinoma with signs of adenocarcinoma or squamous cell carcinoma.
Symptoms of small cell lung cancer
Usually, the first sign of a tumor is a prolonged cough, which is often regarded as a smoker’s bronchitis. An alarming symptom is always the appearance of an impurity of blood in the sputum. Chest pains, shortness of breath, loss of appetite, weight loss, and progressive weakness are also characteristic. In some cases, small cell lung cancer clinically manifests with obstructive pneumonia caused by bronchial occlusion and atelectasis of a part of the lung, or exudative pleurisy.
In the later stages, when the mediastinum is involved in the process, mediastinal compression syndrome develops, including dysphagia, hoarseness of voice due to laryngeal nerve paralysis, signs of compression of the superior vena cava. There are often various paraneoplastic syndromes: Cushing’s syndrome, Lambert-Eaton myasthenic syndrome, syndrome of inadequate secretion of antidiuretic hormone.
Small cell lung cancer is characterized by early and widespread metastasis to the intracoracic lymph nodes, adrenal glands, liver, bones and brain. In this case, the symptoms correspond to the localization of metastases (hepatomegaly, jaundice, spinal pain, headaches, bouts of loss of consciousness, etc.).
Diagnostics of small cell lung cancer
To correctly assess the extent of the tumor process, a clinical examination (examination, analysis of physical data) is supplemented by instrumental diagnostics, which is carried out in three stages. At the first stage, visualization of small cell lung cancer is achieved using radiation methods – chest X-ray, CT of the lungs, positron emission tomography.
The task of the second stage is morphological confirmation of the diagnosis, for which bronchoscopy with biopsy, pleural puncture with exudate sampling, lymph node biopsy, diagnostic thoracoscopy are performed. In the future, the obtained material is subjected to histological or cytological analysis. At the final stage, MSCT of the abdominal cavity, MRI of the brain, and skeletal scintigraphy allow to exclude distant metastasis.
Treatment and prognosis
Clear staging of small cell lung cancer determines the possibilities of its surgical or therapeutic treatment, as well as predicting survival. Surgical treatment of small cell lung cancer is indicated only in the early stages (I-II). But even in this case, it is necessarily supplemented by several courses of postoperative polychemotherapy. In this scenario of patient management, the 5-year survival rate within this group does not exceed 40%.
The remaining patients with a localized form of small cell lung cancer are prescribed from 2 to 4 courses of treatment with cytostatics (cyclophosphane, cisplatin, vincristine, doxorubicin, gemcitabine, etoposide, etc.) in the mode of monotherapy or combination therapy in combination with irradiation of the primary focus in the lung, root lymph nodes and mediastinum. When remission is achieved, preventive radiation of the brain is additionally prescribed to reduce the risk of its metastatic lesion. Combination therapy allows prolonging the life of patients with a localized form of small cell lung cancer for an average of 1.5-2 years.
Patients with locally advanced stage of small cell lung cancer are shown to undergo 4-6 courses of polychemotherapy. With metastatic lesions of the brain, adrenal glands, bones, radiation therapy is used. Despite the sensitivity of the tumor to chemotherapy and radiation treatment, relapses of small cell lung cancer are very frequent. In some cases, the recurrence of lung cancer that has occurred turns out to be refractory to antitumor therapy – then the average survival usually does not exceed 3-4 months.
Literature
- Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Demedts IK, Vermaelen KY, van Meerbeeck JP. Eur Respir J. 2010 Jan;35(1):202-15 link
- Advances in Small Cell Lung Cancer. Kalemkerian GP, Schneider BJ. Hematol Oncol Clin North Am. 2017 Feb;31(1):143-156 link
- Phase II study of accelerated high-dose radiotherapy with concurrent chemotherapy for patients with limited small-cell lung cancer: Radiation Therapy Oncology Group protocol 0239. Komaki R, Paulus R, Ettinger DS, Videtic GM, Bradley JD, Glisson BS, Langer CJ, Sause WT, Curran WJ Jr, Choy H. Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):e531-6. link
- Multidisciplinary management of small cell lung cancer. Goldberg SB, Willers H, Heist RS. Surg Oncol Clin N Am. 2013 Apr;22(2):329-43. link