Lung Cancer - Pathology Flashcards
What are primary lung cancers derived from and what two groups are they classically divided into?
Epithelial origin
Classically divided into Small Cell Carcinoma (SCC) and Non-small cell lung cancer (NSCLC)
What specific cancers fall under the umbrella of non-small cell lung cancer?
- Squamous Cell Carcinoma
- Adenocarcinoma
- Large Cell (Undifferentiated) Carcinoma
Why are carcinoid tumors put into a secondary group?
They are still technically carcinomas, but have a much more indolent course than NSCLC and are not associated with smoking
What primary lung cancers are associated with neuroendocrine features? What is pathoma’s mnemonic for the paraneoplastic syndromes?
Small Cell Carcinoma & Carcinoid Tumor
Pathoma’s mnemonic - if it starts with an S sound / C sound, it is associated with a paraneoplastic syndrome:
SCC, Carcinoid tumors, and Squamous cell carcinoma (NSCLC)
Why is lung cancer so deadly, and why are we hopeful that we can control it better in the future?
Because typically patients present when it is already so advanced in its course
Lung Cancer has a long latency period -> window of opportunity for screening where early cancer may be detected and virtually cured
-also only tends to affect middle aged and elderly
What is the primary risk factor for lung cancer, and a few less important ones?
Cigarette smoking
Others:
Radon exposure, asbestos, and air pollution
What is the most common subtype of lung cancer? What lung cancers have the highest incidence in smokers vs nonsmokers?
Adenocarcinoma is most common
Nonsmokers - primarily adenocarcinoma
Smokers - primarily squamous cell carcinoma, second highest is small cell carcinoma
Of the classical lung cancers, which ones are central vs peripheral? Why?
S = Central
Squamous cell carcinoma and small cell carcinoma tend to be central - arise from respiratory mucosa of main or lobar bronchi
Adenocarcinoma / Large cell carcinoma tend to be peripheral - arise from club cells or Type II pneumocytes - terminal bronchioles / alveoli
Which tumors are most likely to present with pleural effusion / chest pain and distant metastases and why?
Pleural effusion / chest pain - Adenocarcinoma, Large cell carcinoma
-> grow more peripherally
Distant metastases - Adenocarinoma, Large cell carcinoma
-> more distal so they present later
Also small cell carcinoma -> since its so aggressive
What tumors are associated with cough, hemoptysis, stridor, pneumonia, and dyspnea in their presentation?
Squamous cell carcinoma and small cell carcinoma
-> primary tumors which grow more centrally
What is the treatment for small cell carcinoma and why? How do you remember this?
Chemotherapy / radiation is the treatment of choice, because it grows so rapidly it is most affected
Not amenable to surgical resection like NSCLC because the tumor is “so small that the surgeon can’t see them”
What is the only type of lung cancer which currently has targetable molecular alterations? What molecular target is this and who is it seen in?
Adenocarcinoma
Seen in non-smokers and women
Molecular target is EGFR mutations (not seen in other cancers) - EGFR inhibitors
What is the progression of pathogenesis for squamous cell carcinoma?
Normal mucosa -> squamous metaplasia (smoking) -> mild dysplasia -> progress to CIS -> invasive SqCC
What becomes the features of dysplastic cells in SqCC?
Cells become progressively undifferentiated towards the surface, with high N/C ratios and pleomorphism, with mitotic bodies and high proliferative rates
Eventually, squamous differentiation is only seen in the formation of keratin pearls and intracellular bridges
What is the current view of the progression of adenocarcinoma?
- Normal terminal bronchioles / alveoli - Club cells and Type II pneumocytes
- Atypical adenomatous hyperplasia (AAH)
- Adenocarcinoma in situ (AIS)
- Invasive adenocarcinoma
What are the features of atypical adenomatous hyperplasia (AAH)?
Pneumocytes become very large, interstitial space proliferates
-> hyperplasia of Type II!! pneumocytes vs Type I, with increasing N/C ratio and hyperchromasia (density of heterochromatin)
How does invasive adenocarcinoma look, vs AIS?
AIS - thickening of septae with fibrosis and more atypia of cells, but native alveolar IS structure preserved
Invasive Aca - Neoplastic glands are formed, destroying native alveolar structure, with extensive collagen (desmoplasia) and tissue remodeling
Can invasive Aca and AIS coexist?
Yes - relative proportion of invasive Aca vs AIS determines prognosis
-> AIS is a premalignant stage and can be present at the same time
What tumor type is most associated with K-Ras mutations? In what patient population?
Adenocarcinoma
- occurs in smokers
- nonsmokers typically don’t have this mutation, but rather EGFR mutations (described previously)
What mutation occurs in virtually all lung cancers? Is it the same in all patient populations?
p53 mutations
-different mutations between smokers and nonsmokers
What additional mutation is most common in small cell carcinoma which accounts for its invasiveness?
Rb deletions (rapid progression through cell cycle by failure to block E2F-dependent production of cyclin E)
What is the only non-invasive method for tissue diagnosis of malignancy? What lesions does it detect most easily?
Sputum cytology
Most easily detects central tumors - i.e. squamous cell carcinoma, small cell carcinoma
What other invasive methods can be used for tumor sampling, especially peripheral tumors? What is fine needle aspiration vs biopsy?
Transthoracic sampling of lung - for peripheral tumors (highest sensitivity)
Sampling during bronchoscopy - for more central tumors
Fine needle aspiration - sampling yielding cells
Fine needle biopsy - sampling yielding tissue
What forms the intercellular bridges of squamous cell carcinoma?
Desmosomes which cause interlocking of cytoplasmic projections to adjacent cells
In what way are squamous cell carcinomas similar to normal squamous epithelia?
Typically grows in nests, with undifferentiated basal cells in the periphery, and progressive differentiation towards center
-> nests will often cavitate and have an exfoliated center of keratinized cells / necrotic debris.
In what way does adenocarcinoma seem very similar to regular exocrine glands (its differentiation pattern)
Cells arrange around central lumen, like acini, and secrete mucins, or surfactant (normally secreted by club cells / Type II pneumocytes).
What typically has good prognostic value upon identification of an adenocarcinoma?
Growth pattern - i.e. papillary vs acinar vs solid vs micropapillary
What accounts for cytoplasmic vacuolization in adenocarcinoma and how is it definitively told apart from SqCC?
cytoplasmic vacuolization - exocrine differentiation with accumulation of intracellular secretory vesicles (i.e. mucin)
Told apart via immunohistochemistry (SqCC will have keratin)
What is the pathologic morphology of Large Cell Carcinoma and how is it diagnosed?
Poorly differentiated tumor - no keratin pearls, intercellular bridges, exocrine glands, or mucin
-> a diagnosis of exclusion, thorough sampling is required
What are the neuroendocrine tumors and their generally shared morphology? What is the neuroendocrine marker?
Small Cell Carcinoma, and Typical / Atypical Carcinoid tumors
Grow in nests and plates, surrounded by richly vascularized stroma
Neuroendocrine marker - chromogranin
What are the specific features which help you to identify a small cell carcinoma (vs carcinoid)?
Small cell size, with very high proliferative / apoptotic rates, high N/C ratio, fine chromatin (homogenously dispersed), and absent or rare nucleoli
- > Extensive necrosis due to such rapid overgrowth of blood supply
- > molding and crush artifacts
What are the molding and crush artifacts which are so characteristic of small cell carcinoma?
Molding - cells are growing so fast that they leave their expression on the adjacent cell and appear to mold together
Crush artifact - Threads of crushed DNA will be dispersed across the histological slide
What lung neuroendocrine tumor has the best prognosis, and what syndrome is it associated with? Is smoking a risk factor?
Typical carcinoid tumor - associated with Multiple Endocrine Neoplasia 1 (MEN1)
Smoking is not a risk factor for atypical or typical carcinoid tumors
What are the typical symptoms of carcinoid tumors at presentation? How does it relate to the morphology of the tumor?
Hemoptysis, dyspnea, and post-obstructive pneumonia secondary to bronchial obstruction
Tumors tend to grow as exophytic, endobronchial masses
-> remember that S sound indicates central involvement
What are the histological features of typical carcinoid tumor?
Low grade
- > low N/C ratio
- > prominent granular cytoplasm
- > “salt and pepper” fine chromatin distribution with absent or few nucleoli
- > NO necrosis (vs SCC)
- > low proliferative rate
- > still arranged in nets juxtaposed to rich capillary network
What defines something as an Atypical carcinoid tumor?
Has a typical carcinoid morphology, but has EITHER 1. increased mitotic rate or 2. necrosis (typically occurs in punctate, bean-shaped foci)
How does the prognosis of atypical carcinoid tumor compare to the other neuroendocrine tumors?
More aggressive than typical carcinoid -> more LN metastases, and grows larger
Less aggressive than small cell carcinoma -> must be less than 10 mitosis per high power field (no mem #)
