Bronchogenic carcinoma


 * Bronchogenic carcinoma means carcinoma of the bronchi and lung parenchyma.


 * Bronchogenic carcinoma refers to carcinoma of the bronchi and lung parenchyma.
 * Morphologically bronchogenic carcinoma is divided into 2 types:
 * small cell (SCLC)
 * non-small cell bronchogenic carcinoma (NSCLC).
 * SCLC accounts for about 20-25%, NSCLC 75-80%.
 * Non-small cell carcinoma contains 3 subtypes of tumor:
 * squamous cell carcinoma,
 * adenocarcinoma,
 * large cell carcinoma.
 * Lung tumors can also be combined → it contains a component of SCLC and another histological type.

!!! Histological determination of cancer is essential because the prognosis and treatment of small cell and non-small cell carcinomas are diametrically different!

Biological properties

 * Small cell carcinoma (SCLC) → grows rapidly and produces distant metastases early.
 * For this reason, surgical treatment options for the tumor are limited.
 * However, cancer responds well to chemotherapy and radiotherapy.


 * Non-small cell carcinoma (NSCLC)→ grows more slowly than the previous type of tumor, and therefore the tumor can be treated by surgical resection of the tumor.
 * The sensitivity to treatment is lower in this type of tumor.

Epidemiology

 * Worldwide, bronchogenic carcinoma is the most common malignancy in men in incidence and mortality.
 * In women, it ranks third in incidence and second in mortality (after breast cancer).
 * It accounts for 20% of all cancer deaths worldwide.
 * In the Czech Republic, bronchogenic carcinoma has the second-highest incidence (93 / 100,000 inhabitants) among malignant tumors.
 * It has an increasing incidence in the female population and is generally at the level of 60 / 100,000 inhabitants.
 * The highest incidence is between the ages of 70 and 85.

Etiology

 * The influences that cause bronchogenic carcinoma can be divided into endogenous and exogenous.
 * Endogenous effects include increased cytochrome P450 activity (increased production of carcinogens from cigarette smoke), decreased glutathione S-transferase function, decreased activity of cellular DNA repair mechanisms, as well as TP53 gene mutations.
 * The most significant exogenous cause is smoking. 90% of lung tumors are reported to occur in smokers
 * Passive smoking also poses an increased risk.
 * Another risk factor is increased radon exposure.
 * 222Rn is formed by the decay of uranium.
 * In the Czech Republic, there is increased exposure to natural radon in the South Bohemian Region.
 * Other important carcinogens are part of the workload - asbestos, inorganic compounds of arsenic, sulfur, compounds of chromium, nickel, or PVC. Another risk factor is ionizing radiation.

Clinical picture

 * Bronchogenic carcinoma does not show early symptoms.
 * As soon as the symptoms of the disease appear, it is already advanced cancer.
 * We divide the symptoms into three groups: intrathoracic, extrathoracic, and paraneoplastic.


 * 1) Intrathoracic symptoms
 * 2) * Intrathoracic symptoms depend on the size and location of the primary tumor.
 * 3) ** In centrally growing tumors:
 * 4) *** cough (in 45-75% of patients - initially dry, irritating, then productive);
 * 5) *** change like chronic cough (greater intensity, frequency, irritability); hemoptysis (20-30%);
 * 6) *** stridor in narrowing of the main airways;
 * 7) *** bronchopneumonia in bronchial obstruction;
 * 8) *** upper vena cava syndrome as a result of oppression by enlarged lymph nodes;
 * 9) *** hoarseness during compression of the recurrent laryngeal nerve, where paresis of the vocal cords occurs;
 * 10) *** in advanced stages also shortness of breath.
 * 11) ** For peripherally growing tumors:
 * 12) *** chest pain, restrictive dyspnoea.
 * 13) ** Pancoast tumor → a consequence of the local progression of a tumor growing in the lung tip, which may affect:
 * 14) *** plexus brachialis → severe upper limb pain, paresis;
 * 15) *** cervical plexus → Horner's syndrome (miosis, ptosis, enophthalmos) develops.
 * 16) Extrathoracic symptoms
 * 17) * In CNS metastases → headaches, visual impairment, neurological or mental disorders.
 * 18) * In bone metastasis → anemia, leukoerythroblastosis, pain, pathological fractures.
 * 19) * Liver metastases are manifested by jaundice and other hepatobiliary symptoms.
 * 20) Paraneoplastic symptoms
 * 21) * They are very common in bronchogenic carcinomas and can also be the first manifestation of the disease.
 * 22) * Endogenous paraneoplastic syndromes include hypercalcemia and hypophosphataemia in ectopic parathyroid hormone secretion.
 * 23) * Hyponatremia - inadequate ADH secretion.
 * 24) * Cushing's syndrome with hypokalemia in ectopic ACTH secretion.
 * 25) * Hypertrophic osteoarthropathy - clubbed fingers, periostitis.
 * 26) * Dermatomyositis.
 * 27) * Neurological - peripheral neuropathy, muscle myopathy.
 * 28) * Muscle - myasthenia.
 * 29) * Hematological.

Diagnostics

 * We cannot diagnose bronchogenic carcinoma alone based on physical examination and imaging methods.
 * We can determine the definitive diagnosis only based on histopathological examination.
 * For a patient (especially with lung disease), a biopsy is always a burden, so it should be treated only if there is a serious suspicion of cancer.

Physical exam

 * The physical finding is often physiological.
 * Sometimes we can find shortness of breath and shortened percussion, which indicates a pleural effusion.
 * Whistling or squeaking may appear. It is necessary to specifically examine the lymph nodes - the supraclavicular, axillary, and cervical.
 * An enlarged liver may already be metastatic.

Imaging methods

 * 1) X-ray - posterior and lateral projections.
 * 2) CT - lungs and mediastinum.
 * 3) MRI - lungs and mediastinum, suitable for Pancoast's tumor.
 * 4) other → PET, abdomen and retroperitoneum, skeletal scintigraphy, brain CT, sternal puncture.

Cytohistological examination

 * 1) Bronchoscopy → a collection of material for histological examination, using a brush for cytological examination, changes can be evaluated macroscopically.
 * 2) Video-assisted thoracoscopy (VATS) → biopsy/resection of a part of the lung parenchyma.
 * 3) Mediastinoscopy.
 * 4) Transparietal biopsy → under X-ray / CT control (mainly peripheral lesions).
 * 5) Cryobiopsy.

If the patient is not allowed to perform a sampling examination, we can cytologically examine the sputum (3-5 doses).

Small cell carcinoma

 * Oat carcinoma → uniform small cells with a narrow cytoplasmic margin are typical.
 * Intermediate form (spindle cell) → polygonal cells and spindle cell shapes.
 * Small cell carcinomas have a short doubling time, a high growth fraction, and a tendency to early regional and distant metastasis (CNS, bones, liver, adrenal glands, skin).
 * Hilar and mediastinal adenopathy, atelectasis, and secondary bronchopneumonia are more common than non-small cell carcinomas.

Non-small cell carcinoma

 * Squamous cell carcinomas (epidermoid, squamous cell) → central localization, a tendency to early involvement of mediastinal nodes.
 * Adenocarcinomas → peripherally localized, a tendency to both regional and systemic dissemination.
 * Large cell carcinomas → less common, also manifest as peripheral lesions and have the same tendency to metastasize as adenocarcinoma.

Therapy

 * Treatment for small cell and non-small cell forms differs in many respects.


 * 1) Treatment of small cell carcinoma
 * 2) * Chemotherapy, tumor-targeted and metastatic radiotherapy, preventive brain irradiation, and rarely surgery.
 * 3) * In practice, SCLC is divided into 2 forms:
 * 4) ** Limited disease - the disease affects only one pulmonary wing with/without the involvement of ipsilateral or contralateral mediastinal or supraclavicular nodes and with/without ipsilateral effusion, which can be taken up in one irradiation field.
 * 5) ** Extensive diseases - all other forms.


 * The basis of chemotherapy in both forms is chemotherapy for 4-6 cycles of cisplatin + etoposide.
 * Cisplatin can be replaced by carboplatin. Topotecan is used as second-line chemotherapy.
 * In the limited form, radiotherapy is combined with chemotherapy - a standard treatment procedure.
 * Surgical treatment is indicated only in very limited cases. Systemic treatment must always follow.

Treatment of non-small cell lung cancer

 * Determining the clinical stage based on the TNM classification is the basis for determining treatment.


 * In combination chemotherapy, a platinum derivative (cisplatin, carboplatin) with cytostatics III is used. generation (vinorelbine, gemcitabine, paclitaxel).
 * Palliative chemotherapy takes 2-6 cycles.
 * After the 2nd and 4th cycles, the patient's condition is evaluated

Biological treatment of NSCLC

 * Tyrosine kinase inhibitors: erlotinib + gefitinib +afatinib → indicated in patients with a positive activating mutation of the EGFR gene.
 * Due to a mutation in the EGFR gene, the receptor is pathologically activated and the properties that make cells malignant are affected
 * inhibition of apoptosis, angiogenesis, the ability of the tumor to metastasize, uncontrolled cell proliferation
 * Monoclonal antibody against VEGFR: bevacizumab
 * crizotinib → a selective inhibitor of ALK and its oncogenic variants (eg EML4-ALK gene fusion).

Differential diagnostics

 * Other lung tumors.
 * granulomatous lung processes - tuberculosis, sarcoidosis, pneumoconiosis.

Prognosis

 * The prognosis depends on the type and stage of the disease.


 * 1) small cell carcinoma

2. non-small cell carcinoma


 * In stage I, the 5-year survival is 40-50%.
 * In stage II, the 5-year survival is about 30%.
 * Stage III around 10% and stage IV less than 1%.
 * The median survival for recurrent stages II and III are about 2 years.
 * For stage IV, the median is 12 months.

Related articles

 * Malobuněčný karcinom plic (preparát)
 * Nádory plic
 * Pancoastův tumor

Used literature

 * KLENER, Pavel, et al. Vnitřní lékařství. 3. vydání. Praha : Galén, 2006. 1158 s.  ISBN 80-7262-430-X.


 * ČEŠKA, Richard, et al. Interna. 1. vydání. Praha : Triton, 2010. 855 s.  ISBN 978-80-7387-423-0.