Lungs Flashcards
Epidemiology of lung cancers?
Lung cancer is the second most diagnosed but it is the one with highest mortality. Usually diagnosed in old patients and life expectancy is 2 years. The reasons is because the cancer is usually detected when it is already metastatic and patients are not operable.
Type of diagnostic tools used?
When lung neoplasia is suspected CT scans, MRI, bronchoscopy and other procedure may be performed.
Classification of Lung tumors?
- Non Small Cell Lung Cancer like Adenocarcinoma, Squamous Cell Carcinoma and Large Cell Carcinoma.
- Neuroendocrine Tumors like Small Cell Lung Carcinoma, Large Cell Neuroendocrine Carcinoma, Atypical Carcinoid and Typical Carcinoid.
Squamous Cell Carcinoma?
Constitutes 40% of all NSCLC. It is highly associated with tobacco smoke. It has many mutations but the highest frequency is TP53. The tumor is usually centrally located and affects flat cells lining inside the airways usually near the bronchi. Peripheral localization is getting more common due to cigarette smoking. SCC are antedated by metaplasia and dysplasia and it usually spreads through lymph.
Adenocarcinoma of the Lungs? Different types of lesions?
Is the most frequent NSCLC with 60% of cases. Less associated with tobacco, might be associated with pollution. Occur more commonly in women as they are more likely to have EGFR mutation. ADC is usually peripherally located and associated with pleural effusions and distant metastasis.
- Pre invasive lesions : A. Atypical Adenomatous Hyperplasia (AAH) is the precursor lesion (<5mm) characterized by dysplastic pneumocytes that are mildly fibrotic. B. ADC in situ is a lesion less than 3 cm and made entirely of dysplastic cells along alveolar septae. It is usually non mucinous but if it is, it is more aggressive.
- Minimally Invasive ADC : Less than 3 cm. Tumor cells crawl along alveolar septae. Solitary and discrete and can be mucinous or non mucinous.
- Invasive ADC : Heterogeneous histological types of cells, they vary from well differentiated with glandular elements to papillary lesions to solid masses. The majority express thyroid transcription factor 1.
Large Cell Carcinoma
It is an undifferentiated malignant epithelial tumor that lack the cytological feature of other lung cancers. The cells have large and prominent nuclei. It is diagnose though exclusion as it does not express any markers associated with ADC like TTF1 or with SCC like p63 and p40.
Types of neuroendocrine tumors?
NETs arise from cells capable of synthesize and secretion of biologically active substance. They are classified : 1. SCLC which can be pure or combined, 2. Large cell neuroendocrine carcinoma and 3. Typical carcinoid and Atypical carcinoid.
Small Cell Lung Cancer?
Small cell cancer can arise in almost any organ but it is most frequent in the lung. SCLC shows strongest association with smoking, alterations of TP53, RB and MYC. Usually found centrally located but already spread outwards, frequently metastasizes to LNs and organs. Some markers present in SCLC are CK8-18 which is a cytokeratin used to differentiate epithelial cells, TTF1, Synaptophysin + Chromogranin A used to detect cells of neuroendocrine origin. The cells of this tumor have absent or almost absent nuclei, ill defined borders, they can be round, oval or spindle shaped. Mitotic count is high.
Large Cell Neuroendocrine Carcinoma?
Considered a variant of LCC, progression is rapid and aggressive. High mitotic rate. Prognosis not bad as its rapid behavior makes it susceptible to chemotherapy.
What is a carcinoid and what are the different types?
A Carcinoid is a well differentiated neuroendocrine tumor originating in the GI tract, lungs or other primary sites. They are low grade malignant epithelial neoplasm that can be TC or AC.
TC : Fewer than two mitosis mm squared. Lacks necrosis. Highly vascularized thus performing biopsy is dangerous do to possible hemorrhaging. Slow growing tumor.
AC : More aggressive, showing 2 to 3 times more mitosis and areas of necrosis.
Immunohistochemical markers of these tumors are chromogranin A and synaptophysin, Ki67 which is a marker of proliferation.
Clinical manifestations of lung tumors?
The major presenting complains are cough (75%), chest pain (40%), and dyspnea (20%). Not infrequently the tumor is discovered by its secondary spread.
Lung carcinoma is associated with several paraneoplastic syndromes that may antedate the formation of a pulmonary lesions. Some examples are : High levels of gonadotropins causing gynecomastia, calcitonin causing hypocalcemia, inappropriate ADH secretion causing hyponatremia, ACTH producing Cushing syndrome.
Other systemic manifestations of lung carcinomas include the Eaton Lambert Syndrome, Peripheral Neuropathy, Trousseau Syndrome.
Target therapy in lung cancer?
KRAS mutation : One of the most common, specifically in ADC and it has an incidence of 30/40% and it is related to tobacco smoking. KRAS is a gene acting as an on/off switch in cell proliferation.
EGFR mutation : Epidermal growth Factor is most common in ADC especially in non smokers. EGFR is a tyrosine kinase which is activated by specific ligands and growth factors. If mutated it acts as an oncogene. TKIs are used to fight this mutation some examples are erlotinib and osimertinib.
Immunotherapy: Immune checkpoint inhibitors are used to target PD1 and its ligand for example. There are drugs, monoclonal antibodies, which interfere the function by binding with the receptor or ligand. Darvalumab has show to decrease death risk by 32% and Nivolumab and Pembrolizumab are also used in stage 4 cancers.
Idiopathic Pulmonary Fibrosis ?
It is a restrictive lung disease. It refers to a syndrome marked by progressive interstitial pulmonary fibrosis and respiratory failure. The histologic pattern is defined as usual interstitial pneumonia. The root cause is still unknown but there are some implicated factors such as environmental factors like cigarettes, wood dusts and metal fumes, Genetic factors and age as it rarely appears before 50 yr old. Microscopically the hallmark is patchy interstitial fibrosis which varies in intensity, the fibrosis varies in stages, the latter stages cause the destruction of the alveolar architecture. There is also the formation of cystic spaces aka honeycomb lung. The clinical course begins with increasing dyspnea and dry cough. Mean survival is 3 years and the only cure is lung transplantation. Two drugs that slow down the fibrotic process are Pirfenidone and Nintedanib they inhibit VEGFR and FGFR.
Nonspecific Interstitial Pneumonia?
Non specific comes from the lack of diagnostic features from the biopsy of the lung. On the histological basis it can divide in a Cellular Pattern, mild to moderate interstitial inflammation usually in younger patients with good prognosis, and Fibrosing Pattern which is characterized by diffuse or patchy fibrotic lesions at the same stage of development unlike IPF. Clinically patients present dyspnea ad cough for months, more likely to be female smokers in their 60s.
Cryptogenic Organizing Pneumonia?
COP is a synonym of Bronchiolitis Obliterans Organizing Pneumonia, BOOP. Patients present with cough and dyspnea. Histologically it is characterized by the presence of Polypoid Plugs made of loose CT within alveolar ducts, alveoli and bronchioles. They are observable as whitish plaques, the CT is of the same age, no fibrosis and lung architecture is normal. Some patients recover spontaneously, but most need oral steroid for 6 months or longer.
