Microcellular lung cancer (lat. microcellular carcinoma ) is considered different from other, non – microcellular lung cancers due to its clinical and biological characteristics.
Microcellular lung cancer has aggressive behavior with rapid growth, early spread to distant sites, special susceptibility to chemotherapy and radiotherapy, and frequent association with specific paraneoplastic syndromes – because cells Microcellular lung cancer they contain neurosecretory granules (vesicles that contain neuroendocrine hormones).
Surgical care usually does not play an important role in treatment, except in very rare situations. By overall incidence, the third most common histological types of lung cancer are, after adenocarcinoma and squamous cell carcinoma.
The epidemiology of microcellular lung cancer has not changed in recent years. The incidence was about 20-25% of newly diagnosed all lung cancers in the past. It is now about 15%.
Globally, lung cancer is the most common malignancy in men, and the fifth most common cancer in women. According to WHO statistics, just over a million new cases are diagnosed annually worldwide. This is less than expected, probably as a result of a lack of diagnosis or non-reporting of the diagnosis in developing countries. Separate statistics for microcellular carcinoma are not available.
The probability of developing lung cancer in men and women in different age groups is approximately as follows:
- 0-39 years: men 0.03%, women 0.03%;
- 40-59 years: men 0.95%, women 0.79%;
- 60-69 years: men 2.35%, women 1.75%;
- over 70 years: men 6.71%, women 4.83%;
- total from birth to death: men 7.73%, women 6.31%.
As with other histopathological forms of lung cancer, most small cell lung cancers occur in the age group of 35 to 75 years, and the peak incidence is in persons aged 55-65 years.
Etiology of microcellular lung cancer
Smoking, mining (uranium) and exposure to radon are associated with an increased risk of occurrence microcellular lung cancer .
Smoking is the predominant cause of microcellular lung cancer (but also non-microcellular forms). Of all histological subtypes of lung cancer, microcellular and squamous carcinoma have the strongest correlation with tobacco. About 98% of patients with microcellular lung cancer have a history of smoking.
All types of lung cancer are more common in uranium miners, but the microcellular form is the most common. The incidence increases even more if these people smoke at the same time.
Exposure to radon, an inert gas that evolves during decomposition uranium , has also been reported to cause microcellular lung cancer.
Microcellular carcinomas of the lungs (“oat cell carcinomas”) usually occur at peribronchial sites and infiltrate the bronchial submucosa. Metastases occur early in the course of the disease, with frequent spread to the mediastinal lymph nodes, liver, bone, adrenal glands, and brain.
In addition, the formation of different peptides leads to a different range of paraneoplastic syndromes; the most common are syndrome of inappropriate antidiuretic hormone secretion (SIADH) and syndrome of ectopic adrenocorticotropic hormone (ACTH) production. In addition, autoimmune phenomena can lead to various neurological syndromes such as Lambert-Eaton syndrome.
Recent studies have identified oncogene activation and tumor suppressor gene inactivation in microcellular lung cancer. It is not known how important these changes are in the development of microcellular lung cancer. The most frequently mentioned genes are oncogenes of the myc family, but the role of amplification of the myc family of oncogenes requires further research. Also, mutations in the retinoblastoma (RB) tumor suppressor gene were found in almost 60% of small cell lung cancer cases, as well as p53 mutations. tumor suppressor gene , but their exact role is not known.
Signs and symptoms
Patients with microcellular lung cancer often have symptoms such as dyspnea, chronic cough with rapid worsening of symptoms, bone pain, weight loss, fatigue, or even seizures if the patient has brain metastases . Less than 5% of patients have a small asymptomatic primary tumor at presentation.
The disease typically presents with a relatively short duration of symptoms, usually 8.12 weeks before presentation. Symptoms may be the result of local tumor growth, intrathoracic spread, distant spread, and / or paraneoplastic syndromes. Constitutional symptoms include fatigue, anorexia, and weight loss.
Because they are microcellular lung cancers usually centrally located, can cause irritation or obstruction of both major airways. Common symptoms resulting from this are cough, dyspnea and hemoptysis. Squamous cell carcinoma is also presented as a central lesion and sometimes as a cavited lesion.
The tumor may look like a thickening of the mucosa or a tumor mass that annularly covers the entire bronchus. On section, the tumor is grayish-white, partly necrotic and permeated with blood. Microscopically, the tumor consists of tiny oval cells with hyperchromic nuclei and very sparse cytoplasms. The cells may look like oat-cell carcinomas.
Mitoses are numerous in these tumors, and necrosis is common. Tumor cells form large solid clusters. Electron microscopically, the cells contain neuroendocrine granules.
Patients give a brief history of symptoms with a recent onset and rapid exacerbation. Rapid tumor growth can lead to obstruction of the larger airways, with distal collapse and consequent procedural pneumonitis. Fever can be the result of an infection distal to the site of obstruction or the tumor itself.
Microcellular lung cancers grow rapidly and metastasize to mediastinal lymph nodes relatively early in the course of the disease. At presentation, patients may have a large intrathoracic tumor, and distinguishing the primary tumor from lymph node metastases may be impossible. Pressure on mediastinal structures can cause a variety of symptoms.
Symptoms due to intrathoracic spread may include:
- upper vena cava obstruction,
- hoarseness (eg due to paresis of the n.laryngeus recurrens),
- paresis n.frenicusa,
- dysphagia (eg compression of the esophagus),
- stridor (e.g., compression of the main tracheal bronchus).
Microcellular lung cancer causes obstruction of the superior vena cava more often than non-small cell carcinoma, with the resulting syndrome of the superior vena cava (swelling of the face and upper limbs). Compression of the phrenic nerve causes paralysis of the ipsilateral hemidiaphragm, which contributes to respiratory symptoms.
Common sites of metastasis include the brain, bones, liver , adrenal glands and bone marrow. Symptoms depend on where the cancer is spreading. Neurological dysfunction can occur with brain and spinal cord metastases.
Patients with symptomatic brain metastases may have elevated intracranial pressure secondary to lesions, as well as surrounding cerebral edema. These individuals may experience headaches (usually worse early in the morning), blurred vision, photophobia, nausea, vomiting, and a variety of localized symptoms, such as limb weakness.
It is important to recognize vertebral and paraspinal metastases early because, if they are not recognized early, they can potentially lead to permanent loss of neurological functions. It is an oncological emergency. The initial symptom is usually back pain, with or without neurological dysfunction.
The main goal is to diagnose early, before neurological dysfunction. Once poppy is present, neurological dysfunction can progress very rapidly (within a few hours) and cause quadriplegia or paraplegia, depending on the location.
Other symptoms due to distant metastases can cause bone pain due to bone metastases, and abdominal / upper quadrant pain as a result of liver metastases.
Paraneoplastic syndromes are rare disorders triggered by an altered immune response to a neoplasm. The table shows some paraneoplastic syndromes affecting the endocrine and neurological systems.
Findings on physical examination depend on the amount of local spread and distant spread, and the organ system affected. Patients usually experience dyspnea, so physical examination may reveal the use of accessory respiratory muscles (scapular, intercostal).
In addition, due to the nature of the central location of the tumor, patients may develop distal atelectasis and progressive premonium. With pleural effusion, examination reveals mucus on percussion and the absence of breathing sounds on the effusion side.
Pericardial effusions may be asymptomatic when small, or may result in tamponade if large or accumulate over a short period. Patients usually have dyspnea and their heart sounds may be distant on auscultation. Jugular venous pulsations are elevated; paradoxically, they increase with inspiration. Pulsus paradoxus is a classic sign of pericardial tamponade. Tamponade is an emergency condition and requires urgent decompression of the pericardium.
Examination of the extremities may reveal ring fingers, cyanosis, or edema. In the presence of superior vena cava obstruction, the right arm is usually edematous.
Symptoms of brain metastasis
Patients with microcellular lung cancer may have asymptomatic brain metastases in 5-10% of cases. Patients with symptomatic brain metastases may have elevated intracranial talc with concomitant cerebral edema, but physical findings depend on the location of the brain lesion. Fundoscopy should be performed to monitor for signs of elevated intracranial pressure, and a detailed neurological examination should be performed, including evaluation of cerebellar function, coordination, and attitude.
The liver is often the site of spread of small cell lung cancer to the gastrointestinal tract, and jaundice (secondary to biliary outflow blockage by metastasis) or hepatomegaly may be found on physical examination. However, most patients do not have any specific findings related to the GI tract.
Examination of the lymph nodes should be performed with extreme caution. Currently, enlarged ipsilateral supraclavicular lymph nodes are included in the diagnosis of a limited stage, but enlarged axillary lymph nodes mean a diagnosis of a more extensive stage of the disease.
Microcellular lung cancer differs from other types of lung cancer by its rapid growth and propensity for early dissemination. Management of the limited stage of small cell lung cancer includes combination therapy, usually platinum-containing chemostatics, and thoracic radiation therapy.
If the patient achieves complete remission, prophylactic cranial radiation should be offered. The surgical approach plays little, if any, in the management of this type of cancer, except in a small percentage of cases where the cancer is detected very early and is then limited to the lung parenchyma, accidentally resected during surgery due to solitary mass.
Patients with limited stage disease with obvious clinical stage T1 / T2, N0 need mediastinoscopy. If it is negative, they can perform surgical resection with lobectomy, broad resection, or pneumoectomy along with removal of mediastinal lymph nodes.
Management of brain metastases includes high doses of corticosteroids and emergency radiotherapy. Patients with suspected spinal cord compression should receive a dose of intravenous corticosteroids even before sending for MRI. A typical dose is 10 mg dexamethasone IV, followed by 4-6 mg IV / PO every 6 hours.
If the etiological cause of spinal cord compression is known (eg previous diagnosis of microcellular cancer), definitive care is radiotherapy and / or neurosurgical decompression, which should be started without delay.
Given that weight loss and physical activity are important prognostic factors, it is necessary to introduce a quality diet and encourage physical activity.
Approximately 65-70% of patients with microcellular lung cancer have disseminated or extensive disease at presentation. Microcellular lung cancer in the extensive stage is incurable, and the median survival is about 6 weeks. Patients who have localized disease have a median survival of about 12 weeks. These figures refer to untreated patients.
For those treated with multiple chemotherapy and other appropriate therapies, the prognosis is as follows:
- for limited disease 20 months, with a two-year survival of 45% and a five-year survival of 20%,
- for extensive disease, 12 months (an improvement, for example, in 1973, two-year survival was only 1.5%, and in 2000 4.6%).
Indicators of poor prognosis are relapsing disease, weight loss and performance status. Patients who are awake for less than 50% of their normal waking hours, and those with a weight loss of more than 10% over 6 months have a worse prognosis.