Chapter 15: Part 3 (Tumors) Flashcards
Lung and bronchus cancer is the ____ most common cancer in M and W.
What cancer causes the most deaths?
- Lung and bronchus
- Lung and bronchus
How do we describe tobacco years?
Duration and intensity using:
pack-year= (packs smoked per day) * number of years.
What is a pack-year of a patient who smoked 2 packs a day for 30 years?
60 pack-years
Large areas of “benign” respiratory mucosa being mutagenized by exposure to carcinogens in tobacco smoke is known as what?
“Field effect”
What are the 3 most common lung tumors in order?
- 1. Adenocarcinoma (38%)
- 2. Squamous cell carcinoma (20%)
- 3. Small cells neuroendocrine carcinoma (14%)
Which type of lung cancer shows the strongest association with smoking?
Small cell carcinoma
Loss of function mutations in which 2 genes and chromosome are seen with small cell carcinoma of the lung?
- TP53
- RB1
- Chr 3p deletions
Deletions of which 3 chromosomal loci and 3 genes are seen as early events in the squamous cell carcinoma of the lung
- 3p and 9p on CDKN2A gene
- 17p (on of TP53 gene)
- Loss of RB tumor suppressor
Amplification of which gene has been associated with squamous cell carcinoma of the lung?
FGFR1
Loss of function mutations in which 2 genes and chromosome are seen with small cell carcinoma of the lung?
- TP53
- RB
- Chr 3p deletions
Amplification of which gene is associated with small cell carcinoma of the lung?
MYC
What mutations cause Adenocarcinomas?
GOF mutations in growth factor receptor pathways, including r
- RTK mutation = EGFR + ALK + ROS + MET and RET
- Non-RTK = KRAS
Which type of lung cancer occurs in the peripheral lung and which in the central/hilar lung?
- Peripheral: adenocarcinoma ; thus most cancers occur peripherally
- Central/hilar: squamous cell carcinoma
What are the 4 stages of lung adenocarcinoma progression?
- 1. Normal
- 2. AAH (atypical adenomatous hyperplasia)
- 3. AIP (adenocarcinoma in-situ)
- 4. Adenocarcinoma
What stage of adenocarcinoma progression is this?
How big?

AAH (atypical adenomatous hyperplasia)
- Dysplastic pneumocytes that line alveoli with with some intersitial fibrosis.
- 5mm or less
What stage of adenocarcinoma progression is this?
How big?

Adenocarcinoma in situ
- Dysplastic cells merging (cofluently) along alveoli
- < 3cm
What stage of adenocarcinoma progression is this?

Invasive pulmonary adenocarcinoma
Malignant glands are invading lung tissue (all glands look different).
Can arise from precursors or new
Do precursor adenocarcinoma lesions all lead to malignancy?
NO
What is the most common lung cancer in non-smokers?
Pulmonary adenocarcinoma
Majority of adenocarcinomas of the lung express which transcription factor required for normal lung development?
Thyroid transcription factor-1
Adenocarcinomas tend to grow ______ than squamous cell carcinomas but metastize _____
slower
earlier
Which tumor of the lung tends to spread by air, forming satellite tumors on alveoli and may consolidate an entire lobe mimicking lobar pneumonia?

Mucinous ADENOCARCINOMA
What is this?

Squamous cell carcinoma with characteristic KERATIN PEARLS
Whatis the progression of squamous cell carcinoma?
NL pseutostratf ciliary columnar epi => squamous cells

Squamous cell carcinoma
MCC in M/F
Stronly assx w ______
Where in the lung does it occur?
Male
Smoking
Centrally; because precursor cells are located in airways and hilum
How do we recoginize squamous cell carcinoma on CYTOLOGY?
Orange cytoplasm is keratin => SQUAMOUS CARCINOMA
Anytime you see ORNG, think squamous carcinoma

What is this?

Small cell neuroendocrine carcinoma
Small cell neuroendocrine carinoma
- lung tumor is almost always ______ at time of presentation, strongly associated with _____ and is best treated with specific chemotherapies/radiation?
Metastatic (so fast that on scans, you DO A WHOLE BODY SCAN)
Smoking
What is the most aggressive lung tumor with no known preinvasive phase?
Small cell *neuroendocrine* carcinoma
What is the histology of the chromatin, cytoplasm, nucleus, and nucleoli like with small cell carcinoma of the lung?
- -Tightly packed small blue cells (d/t chromatin)
- Nuclear molding w nuclei smushed together
- No nucleoli
- Necrotically active
How does small cell carcinoma respond to chemo?
responds, but recurrence is high
If someone has adenocarcinoma, what tests will you run?
-
1. Test for a EGFR mutation.
- -Yes=> treat with a EGFR TK-inhibitor.
- If no => check for ALK rearrangement
* - Yes => treat with Crizotinib.
- If no => check for ALK rearrangement
- If no, treat with chemotherapy w/or w/o Bevacizumab
What is that MOA of Crizotinib?
Inhibits the ALK-EML4 fusion gene.
Tumor immunotherapy attempts to do what?
Block PD-1 or CTLA-4 signaling.
Tumor can acquire PD-1 ligand/CTLA4, bind to T-cell of DC and prevent them from attacking it. Tumor immunotherapy attempts to prevent this interaction so we can kill tumor cells
What drugs to treat adenocarcinomas target EGFR?
- 1. Erlotinib
- 2. Gefinitib
What drugs to treat adenocarcinomas target PD-1/PD-L1?
Pembrolizumab
What drugs to treat adenocarcinomas target CTLA-4?
Ipilimumab (Yervoy)
What drugs to treat squamous cell carcinomas?
You need to be cautious on what drugs to use (VEGF inhibitors) because these occur centrally and we are still seeing what to use bc they are so close to BV.
Release of PTHrP leading to paraneoplastic hypercalcemia is associated with what type of lung tumor?
Squamous cell carcinoma
What paraneoplastic conditions does small cell carcinoma cause?
- SIADH (secrete too much ADH)
- Cushings syndrome (too much ACTH secretion)
What is a dermatologic manfiestation that may be associated with lung tumors?
Acanthosis nigricans
Apical lung cancers (pancoast tumors) in the superior pulmonary sulcus tend to invade which neural structures around the trachea and produce what signs/sx’s?
- Invade cervical sympathetic plexus
- Severe pain in the distribution of the ulnar nerve
- Horner syndrome –> enophthalmos (sunken eyeball) + ptosis (eyelid droop) + miosis (small pupil) + anhidrosis (no sweating on that side of face).
What are 2 hematologic abnormalities that may be assocaited with lung tumors?
- Leukemoid rxns
- Trousseau syndrome (DVT and thromboembolism)
Lambert-Eaton Syndrome is most often associated with what tumor of the lung?
Trousseau sign (migratory thrombophlebitis) is most often associated with what type of lung tumor?
Small cell carcinoma
Adenocarcinoma
What are the spectrum of NE tumors?
1. DIPNECH
2. Carcinoid tumor
3. Atypical carcinoid tumor
What is the main difference between Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) and Carcinoid tumors?
- SIZE!!!
- DIPNECH = very small, <5mm —> “Tumorlets”
- Carcinoid tumor = 5mm or larger
Why is it important to differentiate DIPNECH from Carcinoid tumors?
Carcinoid tumors have ability to metastasize
Are carcinoid tumors benign or malignant?
MALIGNANT!
They are a grade 1 NE carcinoma.
What are features of atypical carcinoid tumors which differ from typical carcinoid tumors (grade 1)?
- 1. Grade 2
- 2. Increased mitotic activity
- NECROSIS (Carcinoids do not undergo necrosis)
- 4. Disordered growth
- Increase rate of metastasis with LOWER survival, but still better than small cell carcinoma.
Can all NE tumors produce a carcinoid syndrome?
Yes
Which cancers are almost always treated w chemotherapy, because they are almost always metastic at presentation?
Small cell lung carcinomas
Which lung cancer is best known to cause paraneoplastic syndromes?
Small cell
Which tumor of the lungs grows as fingerlike or spherical polypoid masses that commonly project into the lumen of the bronchus and may produce so-called collar-button lesions?
Carcinoid tumor
Immunohistochemical stains of carcinoid tumors may be positive for what 4 markers?
- 1. 5HT
- 2. Neuron specific enolase
- 3. Calcitonin
- 4. Bombesin
What are the sx’s of Carcinoid Syndrome?
- - Flushing
- - Diarrhea
- - Cyanosis
What is the prognosis like for typical carcinoid vs. atypical carinoid tumors?
- Typical have 5-year survival of 95%
- Atypical have 5-year survival of 70%
What is a feature that can be seen on CXR and CT indicates a metastatic malignancy?
Multiple discrete nodules (cannonball lesions) scattered throughout all lobes

What are these?

Cannonball lesions (more often located peripherally), meaning this person has a metastatic malignancy
What is this

Pulmonary harmatoma: BENIGN nodules of CT (often hyalinized cartilage, fat or fibrous tissue) surrounded by clefts of respiratory epithelium
LOOKS LIKE MARBLE and has SMOOTH EDGES
Lymphangioleiomyomatosis is a lung disorder occurring almost exclusively in whom?
Young women (VERY UNCOMMON in men)
Lymphangioleiomyomatosis (LAM) is characterized by proliferation of which cells and what does this create morphologically?
Perivascular epithelioid cells –> proliferate and form cysts filled with air.
What are 2 complications of LAM?
- Obstruct lymph vessels
- Cysts can pop and cause a sponatneous pneumothorax.

What is the mutation seen in LAM?
LOF mutation in TSC2, a tumor supressor of mTOR activity
Which markers are expressed by Lymphangioleiomyomatosis?
PEC cells are modified smooth muscle cells and + for melanoma marker HMB-45
The strong tendency for Lymphangioleiomyomatosis to affect young women suggests what hormone contributes to proliferation of perivascular epithelioid cells?
Estrogen
What are the 2 types of pleural effusions?
- 1. Exudate (inflammatory) pleural effusion
- 2. Transudative (non-inflammatory) pleural effision
What is this?

Pleural effusion
What are the major causes of transudate pleural effision?
1. HF, d/t increased hydrostatic pressure
2. Decreased plasma oncotic pressure
What are the major causes of exudative pleural effision?
Inflammation or malignancy
- Infection (TB/bacterial pneumonia)
- PE
What causes pleural effision look like d/t an obstructed duct or in pleural space and most commonly seen in post-surgical CAB.
Milky chylous effusion= chylothorax
What is empyema?
Inflammatory exudate where pus accumulates in the pleural space, often d/t a bacterial infection. It creates web-like traps for fluid, making it hard to remove by draingage
What does fluid in empyema look like?
Thick, yellow with neutrophils and bacteria
what is this

empyema; loculations caused by it
Bloody effusion: be aware of ______
Clear yellow effusion: be aware of ______
Milky Chylous effusion: be aware of _____
- adenocarcinoma
- CHF
- post-surgical CAB or blockage of thoracic duct
Pneumothorax is most commonly associated with what 3 conditions?
- Emphysema
- Asthma
- Tuberculosis
Primary (idiopathic) penumothorax most often occurs in which age group and is due to what?
- Young patients
- Rupture of subpleural blebs
What conditions did we learn that cause a pneumothorax?
- LAM
- LCH (langerhan cells histiocytosis)
what is this

Solitary fibrous tumor: benign soft-tissue tumor in the pleura that is attached to the lung by a pedicle.
Whorls of [reticulin], [collagen fibers] with spindle cells that look like fibroblasts
How does the behavior of Solitary Tumor Cells change when they are small vs when they are larger?
- Small: benign
- Larger: sarcoma
what is this?

solitary fibrous tumor (well DEFINED/circumscribed)
name a malignant pleural tumor
mesothelioma
what cell we find in mesothelioma
ferruginous bodies
Pleural cavity pressure > atmospheric = _____ pneumothorax
tension pneumo
Pleural cavity pressure < atmospheric = _____ pneumothorax
primary pneumothorax
What stain can we easily see solitary fibrous tumors with, benign tumors of the pleura.
CD34
how can we get asbestos => causing mesothelioma?
- insulation
- shipyard workers
- construction workers