Lung 3 Flashcards
T or F
metastatic tumors are more
common than primary tumors.
Tru
In the primary tumors, 90% of the tumors in the
lungs are actually
Carcinomas
The rest of the tumors in the lungs would be
carcinoids,
mesenchymal tumors, and other rare tumors.
is currently the most frequently
diagnosed major cancer and the most common
cause of cancer mortality worldwide.
Lung cancer
Lung cancer is generally a disease of older adults,
occurring most often between ages ________, with a peak incidence
between________________
55
and 84 years
65 and 74 years.
Only __ of all cases occur before the age of 40
2%
is the most common risk
factor that has an established association with
lung cancer
Cigarette smoking
T or F
there is a nearly linear correlation between the
frequency of lung cancer and pack-years of
cigarette smoking.
T
other factors that interact with smoking to predispose individuals to this deadly disease
acquired mutations, genetic makeup of the individual
T or F
women are
more susceptible to carcinogens in tobacco than
men.
T
industrial hazards which increase the risk of developing lung cancer
asbestos,
arsenic, chromium, uranium, nickel, vinyl
chloride and mustard gas
T or f
High-dose ionizing radiation is carcinogenic
T
weakly radioactive, but lung cancer
rates among nonsmoking _____ miners are
four times higher than those in the general
population
Uranium
Asbestos workers who do not smoke
have a______ greater risk of
developing lung cancer
five-fold
asbestos + smoke
55-fold greater risk
Chronic exposure to air particulates in smog may cause
lung irritation, inflammation, and repair, and
you will recall that chronic inflammation and repair
increases the risk of a variety of cancers
is a ubiquitous radioactive gas that has been linked
epidemiologically to increased lung cancer in uranium miners.
Radon gas
T or F
Most of the mutations are acquired.
T
Smoking-related carcinomas of the lung arise by
a stepwise accumulation of
oncogenic “driver” mutations that result in the neoplastic transformation of pulmonary
epithelial cells
Receptor Tyrosine Kinases
- EGFR – 10-15%
- ALK – 3-5%
- ROS1 – 1%
- MET – 2-5%
- RET – 1-2%
most common (Receptor tyrosine kinases)
EGFR
ALK
Positive KRAS is associated with
poor prognosis
Serine/Threonine kinases
BRAF
P13K
KRAS
Oncogenic gain of function mutations
Adenocarcinomas
is the most
common subtype in never-smokers
adenocarcinomas
Chromosome deletions of tumor
suppressor loci
SQUAMOUS CELL CARCINOMAS
site for CDKN2A gene, associated
with P16 mutation
3P9P
site of TP52 gene; associated with
TP53 mutations and p53 protein
overexpression
17p
a gene encoding the
fibroblast growth factor receptor tyrosine kinase.
Amplification of FGFR1
virtually always smoking related and has the
highest mutational burden among lung cancers
● SMALL CELL CARCINOMA
Acquisition of RB loss of function mutations
Small cell carcinoma
Non-small cell carcinomas are your
adenocarcinoma and squamous cell
carcinoma
is seen even in histologically normal lung epithelium, suggesting that this also is a critical early event
Loss of chromosome 3p
Small cell carcinoma
TP53 and RB activation
Acquisition of RB loss of function mutations
Transformation of non-small cell carcinoma to small cell carcinoma
Loss of chromosome 3p
○ Amplification of MYC gene family
mutations in lung cancer (never-smokers)
EGFR mutations
TP53 mutations
Four types of morphologic precursor epithelial
lesions are recognized:
○ Atypical adenomatous hyperplasia ○ Adenocarcinoma in situ ○ Squamous dysplasia and carcinoma in situ ○ Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
T or F
Currently it is not possible to distinguish
between precursor lesions that progress and
those that remain localized or regress.
T
Tumor classification (Adenocarcinoma)
Lepidic, acinar, micropapillary, papillary, solid
Invasive mucinous adenocarcinoma
Minimally invasive adenocarcinoma (nonmucinous, mucinous)
Tumor classification (squamous cell carcinoma)
Keratinizing, nonkeratinizing, basaloid
Tumor classification (Neuroendocrine tumors)
Small cell carcinoma Combined small cell carcinoma Large cell neuroendocrine carcinoma Combined large-cell neuroendocrine carcinoma Carcinoid tumor (typical, atypical)
Tumor classification (Other uncommon types)
Large cell carcinoma Adenosquamous carcinoma Sarcomatoid carcinoma Lymphoepthelioma-like carcinoma and NUT carcinoma Salivary gland-type tumors
mixtures of histologic patterns,
even in the same cancer
○ squamous cell carcinoma and
adenocarcinoma (14%)
○ small cell and squamous cell carcinoma
(5%)
Epithelium of Atypical adenomatous hyperplasia
cuboidal, and there is mild interstitial fibrosis.
ATYPICAL ADENOMATOUS HYPERPLASIA is A small precursor lesion (≤5 mm) characterized
by________ lining alveolar
walls that are mildly fibrotic.
dysplastic pneumocytes
formerly called bronchioloalveolar carcinoma
ADENOCARCINOMA IN-SITU
ADENOCARCINOMA IN-SITU
lesion that is_____ in size and is
composed entirely of _______ growing
along pre-existing alveolar sept
less than 3 cm
dysplastic cells
T or F
In adenocarcinoma in-situ, The cells have more dysplasia than atypical
adenomatous hyperplasia and may or may not
have intracellular mucin
T
Most common form of lung cancer in women
and men
adenocarcinomas
is an invasive malignant epithelial tumor with glandular differentiation or mucin production by the tumor cells
Adenocarcinomas
poorly differentiated
type of adenocarcinoma. It is already difficult to
differentiate with the squamous cell carcinoma.
Hence, we usually end up diagnosing it just like
non-small cell carcinoma.
Solid adenocarcinoma
Lung carcinomas may arise in the
peripheral lung (more often adenocarcinomas) or in the central/hilar region (more often squamous cell carcinomas)
They vary histologically from well-differentiated
tumors with obvious glandular elements (Fig.
15.43A), to papillary lesions resembling other
papillary carcinomas, to solid masses with only
occasional mucin-producing glands and cells
adenocarcinomas
In adenocarcinoma, The majority express ___________, a protein first identified in the
thyroid that is required for normal lung
development.
thyroid transcription
factor-1 (TTF-1)
For _________, we usually request for TTF-1 as an immunohistochemical stain to mark that
this is a adenocarcinoma instead of squamous
cell carcinoma
solid patterns
At the periphery of the tumor there is often a ___ pattern of spread, in which the tumor
cells “crawl” along normal-appearing alveolar
septa.
lepidic
Tumors (≤3 cm) with a small invasive
component (≤5 mm) associated with scarring
and a peripheral lepidic growth pattern are
called
microinvasive adenocarcinoma
variant
where the major component shows papillary
growth pattern, often with complex secondary
and tertiary branching structure. The tumor cells
are arranged in multiple layers around true
fibrovascular cores.
Papillary adenocarcinoma of lung
tend to spread
aerogenously, forming satellite tumors; thus,
these are less likely to be cured by surgery.
Mucinous adenocarcinomas
Mucinous adenocarcinomas may present as a solitary nodule or as multiple nodules, or an entire lobe may be consolidated by tumor, mimicking _______
lobar pneumonia
a variant where
the major tumor component consists of solid
sheets and lacks other recognizable patterns of
adenocarcinoma such as lepidic, acinar, papillary, or micropapillary growth.
Solid adenocarcinoma
T or F
squamous cell carcinoma is more common in men and is strongly associated with smoking
T
are often antedated
by squamous metaplasia or dysplasia in the
bronchial epithelium, which then transforms to
carcinoma in situ
Squamous cell carcinomas
When it is associated with smoking, it starts as
______ in the bronchi associated gene
mutation and eventually it develops into a n
invasive cancer
dysplasia
Squamous cell carcinoma has a different growth pattern. It can protrude into the lumen of the bronchus and can cause obstruction of the airway. Whatever is obstructed would have
secondary atelectasis
T or F
Squamous cell carcinoma can invade the lung parenchyma
T
How to differentiate adenocarcinoma vs Squamous cell carcinoma
Through biopsy
Aside from production of keratin pearls, another
thing that can guide you to the differentiation or
identification of Squamous Cell Carcinoma
differentiation would be the presence of your
intercellular bridges
they are present in well
differentiated or at least differentiated squamous
epithelium
desmosomes
Squamous Cell Carcinoma s are associated with
your ____and ___ for poorly differentiated
Squamous Cell Carcinoma
p63; p40
oat cell
Small cell carcinoma
T or F
Majority of the Small Cell Carcinoma are highly
malignant and there’s a very strong relationship
to cigarette smoking.
T
Most of these tumors arise in the bronchi and
there is no known preinvasive phase.
small cell carcinoma
T or F
Among the malignant lung CA, small cell carcinoma is the most
aggressive and you have a really high mitotic count.
T
This is also the tumor associated with extensive necrosis
Small cell carcinoma
In small cell carcinoma, cytoplasm is ____
very scanty
what pattern is present in the nuclei of small cell carcinoma
chromatin (salt and pepper)
crushed
hyperchromatic cells wherein you can no longer
see them as individual cells.
crushing artifacts (very fragile)
Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells
Azzopardi effect (small cell carcinoma)
electron microscopy
for small cell carcinoma shows
dense-core
neurosecretory granules, about 100 nm in
diameter, in two-thirds of cases of small cell
carcinoma.
suggest that Small cell carcinoma
originates from neuroendocrine progenitor cells,
which are present in the lining bronchial
epithelium.
occurrence of
neurosecretory granules; the expression of
neuroendocrine markers such as
chromogranin, synaptophysin, and CD56;
and the ability of some of these tumors to
secrete hormones (e.g., parathormone-related
protein, a cause of paraneoplastic
hypercalcemia)
they are made up of large cells, and the cells that you see are undifferentiated
Large cell carcinoma
You should do immunohistochemical staining
first before you proceed to a Large cell
carcinoma diagnosis because
they are usually
negative for your markers:
○ adenocarcinoma - TTF-1, napsin A
○ squamous cell carcinoma - p40, p63
has molecular
features similar to those of small cell carcinoma,
but is comprised of tumor cells of larger size
large cell
neuroendocrine carcinoma
T or F
Any type of lung carcinoma may extend to the
pleural surface and then spread within the pleural cavity or into the pericardium
T
Metastases to the
________ can be found in most cases
bronchial, tracheal, and mediastinal nodes
Distant spread of lung carcinoma occurs through
both ______ and ________pathways
lymphatic; hematogenous
may be the first manifestation of an
underlying occult pulmonary lesion.
Metastasis
No organ or tissue is spared, but the a_____, for obscure reasons, are involved in
more than half of the cases.
adrenal glands
liver
30-50%
brain
20%
bone
20%
Anterior mediastinum
Thymoma Parathyroid tumors Teratoma Metastatic carcinoma Lymphoma Thyroid lesions
Posterior mediastinum
Neurogenic tumors Lymphoma Metastatic tumor Bronchogenic cyst gastroenteric hernia
Middle mediastinum
bronchogenic cyst
pericardial cyst
lymphoma
partial obstruction
focal emphysema
90% total obstruction
atelectasis
Impaired drainage of the
airways
Severe suppurative or Ulcerative bronchitis
or bronchiectasis
- sometimes call attention
to an otherwise silent carcinoma.
pulmonary abscess
Superior Vena Cava Syndrome - compression
or invasion of the superior vena cava can cause ________
venous congestion and edema of the head and
arm and, ultimately, circulatory compromise
extension into the
pericardium and pleura
pericarditis and pleuritis
○ Apical lung cancers in the superior pulmonary sulcus
○ Invade the neural structures around the
trachea, including the cervical sympathetic plexus
Pancoast tumors
Produce a group of clinical findings that includes severe pain in the distribution
of the ulnar nerve and Horner syndrome (enophthalmos, ptosis,
miosis, and anhidrosis) on the same side as the lesion
Pancoast tumors
Involvement of central airways
cough
hemorrhage from tumor in airways
hemoptysis
extension of tumor into mediastinum, pleura, or chestwall
chest pain
airway obstruction by tumour
Pneumonia, abscess, lobar collapse
tumor obstruction; accumulation of cellular lipid in foamy macrophages
lipoid pneumonia
tumor spread into pleura
Pleural effusion
recurrent laryngeal nerve invasion
hoarseness
esophageal invasion
dysphagia
phrenic nerve invasion
diaphragm paralysis
chest wall invasion
rib destruction
SVC compression by tumor
SVC syndrome
sympathetic ganglia invasion
horner syndrome
pericardial involvement
pericarditis, tamponade
backpain
bone metastases
headache, hemiparesis, cranial nerve damage,
and seizures
brain metastases
We usually proceed with _________ to determine metastasis
bone scanning,
PETscan
are very sensitive to
chemotherapy and radiotherapy this is
secondary to having very young tumor cells and
you have a lot of tumor cell undergoing
metastasis hence they are very sensitive to
radiation
small cell carcinomas
