Chapter 13: Lung tumors Flashcards
Carcinoma is a tumour that develops from *endothelial/epithelial* cells
Epithelial
What types of tumors are most common in lung tumors?
95% are carcinomas (the remaining 5% span a miscellaneous group that includes carcinoids, mesenchymal malignancies, lymphomas and a few benign lesions)
What is the most common benign lung tumour?
A spherical, small, discrete hematoma that often shows up as a so-called “coin lesion” on chest imaging (consisting of mature cartilage admixed with fat, fibrous tissue and blood vessels)
Carcinoma of the lung is the *least/most* important cause of cancer-related deaths in industrialized countries
most
In a ranking of incidence of cancers, at what place is lung cancer in males and females?
4th in place for both genders (colon (3rd), skin (2nd) and prostate/breast (1st) are above it)
What is the 5-year survival rate
45%
What are the four major histologic types of carcinomas of the lung?
Adenocarcinoma, squamous cell carcinoma, small cll carcinoma (a subtype of neuroendocrine carcinoma) and large cell carcinoma
Which histologic cell types have the strongest association with smoking?
Squamous cell and small cell carcinomas, but there is also an association with adenocarcinoma (although it is more common in non-smokers)
Fill in: Like other cancers, smoking-related carcinomas of the lung arise by a stepwise accumulation of driver … that result in transformation of benign progenitor cells in the lung into neoplastic cells possessing all of the hallmarks of cancer
mutations
Before 2015 (when the WHO introduced a new classification), carcinomas were classified into: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Why was that?
By the time SCLCs were diagnosed, virtually all have metastasized, thus chemotherapy is used. NSCLCs are more likely to be resectable and usually respons poorly to conventional chemotherapy
Why was there a reorganization of the classification of lung tumors in 2015?
There are new therapies available that target specific onco-proteins that are found in subset of NSCLC (mainly adenocarcinomas). Thus, if adequate tissue is available, NSCLC is subjected to molecular analysis to determine if targeted therapy is warranted. In addition, new immunotherapy approaches are now approved for a subset and are being tested in SCLC
The sequence of molecular changes is not random but tends to follow a sequence that parallels the histologic progression toward cancer. Explain these steps. (I don’t think you’re supposed to learn this (like 75% sure))
Inactivation of the putative tumor suppressor genes located on the short arm of chromosome 3 (3p) is a very common early event, whereas mutations in the TP53 tumor suppressor gene and the KRAS oncogene occur relatively late. Certain genetic changes, such as loss of chromosomal material on 3p, are found even in benign bronchial epithelium of smokers without lung cancer, suggesting that large areas of the respiratory mucosa are mutagenized by exposure to carcinogens (“field effect”). On this fertile soil, those cells that accumulate additional mutations ultimately develop into cancer.
A subset of adenocarcinomas (about 10% in whites and 30% in Asians), particularly those arising in nonsmoking women, harbor mutations that activate the epidermal growth factor receptor (EGFR). What does this EGFR do?
It is a tyrosine kinase receptor that stimulates downstream pro-growth pathways involving RAS, PI3K and other signaling molecules
With regard to carcinogenic influences, there is strong evidence that … and, to a much lesser extent, other environmental carcinogens are the main culprits responsible for the mutations that give rise to lung cancers
smoking (you should know this by now ;))
Is there a linear correlation between the frequency of lung cancer and pack-years of cigarette smoking?
Yep (The increased risk is 60 times greater among habitual heavy smokers (two packs a day for 20 years) than among nonsmokers)
True/false: Men are more susceptible to carcinogens in tobacco smoke than woman
False, woman are more susceptible than men (though for unclear reasons)
Is is likely that the mutagenic effect of carcinogens is modified by hereditary (genetic) factors? Why?
Yes, very! Recall that many chemicals require metabolic activation via the P-450 monooxygenase enzyme system for conversion into ultimate carcinogens. Individuals with certain polymorphisms involving the P-450 genes have an increased capacity to activate procarcinogens found cigarette smoke, and are thus exposed to larger doses of carcinogens and incur a greater risk of developing lung cancer. Similarly, individuals whose peripheral blood lymphocytes undergo chromosomal breakages after exposure to tobacco-related carcinogens (mutagen sensitive genotype) have a greater than 10-fold increased risk for developing lung cancer over control subjects.
The sequential changes leading development of squamous cell carcinomas are well documented; there is a linear correlation between the intensity of exposure to cigarette smoke and the appearance of ever more worrisome epithelial changes. What does this begin with and how does it progress?
It begins with rather innocuous basal cell hyperplasia and squamous metaplasia and progress to squamous dysplasia and carcinoma in situ, before culminating in invasive cancer
Carcinomas of the lung begin as small lesions that are *firm/soft* and *grey-white/red-white*
firm and grey-white
Where are adenocarcinomas usually located?
peripherically, but also may occur closer to the hilum
Do carcinomas or adenocarcinomas grow slower?
Adenocarcinomas
Which subtype is more likely to metastasize widely?
Adenocarcinomas (though they grow the slowest and form smaller masses)
What variety of growth patterns can occur in adenocarcinomas?
Acinar (gland-forming), papillary, mucinous and solid types
Precursor lesions of squamous cell carcinomas are shown in this figures. What are the subtypes displayed in the figures?
- (A to C) Some of the earliest (and “mild”) changes in smoking-damaged respiratory epithelium include
- goblet cell hyperplasia (A),
- basal cell (or reserve cell) hyperplasia (B),
- squamous metaplasia (C).
- (D) More ominous changes include the appearance of squamous dysplasia, characterized by the presence of disordered squamous epithelium, with loss of nuclear polarity, nuclear hyperchromasia, pleomorphism, and mitotic figures.
- (E and F) Squamous dysplasia may, in turn, progress through the stages of mild, moderate, and severe dysplasia. Carcinoma in situ (CIS) (E) is the stage that immediately precedes invasive squamous cell carcinoma (F). Apart from the lack of basement membrane disruption in CIS, the cytologic features of CIS are similar to those in frank carcinoma.
Name some differences between small and non-small cell lung carcinoma
Don’t learn by heart, but you should be able to recognize this
