Lung Tumors Flashcards
What is the most significant risk factor for developing lung cancer?
cigarette smoke
What is the most common lung tumor?
adenocarcinoma
most common in men, women & never smokers
In addition to cigarette smoke, what are the most common risk factors associated with lung cancer?
Asbestos
Arsenic
Uranium
Ionizing radiation
pollution
pre-existing inflammatory lung disease
What is an adenocarcinoma?
invasice epithelial tumor with glandular differentiation and/or mucin production
Adenocarcinmoma most commonly affects whats demographic?
non-smoking women
What are the gross features of an adenocarcinoma?
Microscopic organizations?
- Gross
- peripheral scar with pleural puckering
- Micro
- lipedic predominant
- acinar predominant
-
(micro)papillary predominant
- poor prognosis
- solid
- mucinous
What does lipedic predominant mean when describing an adenocarcinoma?
you have an invasive adenocarcinoma that is a small part of the lesion & the bulk of the lesion is actually non-invasive (atypical cells hanging onto alveolar septa)
“butterflies on a treebranch”
treebranch is alveolar septa & butterflies are the atypical cells
What type of lung tumor is shown in the provided image?
Identify its characteristic features.
- Bottom right
- micropapillary variant
- tufts of papillae
- Grossly
- big, white, grey mass that is out toward the periphery
- dip on right border = puckering
- all others -
- glands
- cribiform (pierced by many small holes)
What are the two associated/precursor lesions to adenocarcinoma?
What do they have in common?
- Atypical adenomatous hyperplasia
- Adenocarcinoma I-Situ
both entirely lipidic in growth
Describe the features of atypical adenomatous hyperplasia.
- 5mm of less
- cytologically mildly to moderately atypical pneumocytes admixed with cilliated and goblet cells
- note cell on the alveolar septa with abundant mucin in cytoplasm
- diagnosis not made w/o disclaimer b/c cannot varify there is not verify there is not an invasive componenet
Describe the features of adenocarcinoma In-Situ.
- less than 3cm
- monotonous population of cells with “more atypia than AAH” but still entirely lipedic growth
- cells that have large nucleus hanging on alveolar septa
- diagnosis not made on biopsy w/o disclaimer b/c cannot varify there is not verify there is not an invasive componenet
What are the two stains used to diagnose adenocarcinoma?
- TTF-1 (thyroid transcription factor)
- positive for primary adenocarcinoma of the lung
- negative for all other adenocarcinoma metastasis to the lung (other than thyroid)
- example in provided image
- Napsin A
What two mutations are associated with adenocarcinoma?
- Gain of function mutations involving GF signaling pathways (mutually exclusive)
- Receptor Tyrosine Kinase (TK) (have a drug for that!)
- tend to occur in never smokers
- EGFR
- ALK
- tend to occur in never smokers
- KRAS (poor prognostic)
- Receptor Tyrosine Kinase (TK) (have a drug for that!)
What is squamous cell carcinoma?
It most commonly affects what demographic?
Where do they most common in occur in the lung?
- invasive epithelial tumor characterized by evidence of squamous differentiation
- Demographic
- male smokers
- Location
- central - sub segmental bronchi
- peripheral are on the rise
Why is important to differentiate between squamous cell carcinoma & adenocarcinoma?
- bevacizumab - used to treat adenocarcinoma- can cause serious pulmonary hemorrahage in squamous cell carcinoma
Describe the gross growth patterns & appearance of squamous cell carcinoma.
- Appearance
- grey-white, firm cut surface
- often centrally necrotic +/- cavitation
- Growth patterns
- exophytic endobronchial mass
- obstruction, atelectasis, infection
- peribronchiolar spread
- mediastinal disease
- nodular intraparanchymal mass
- exophytic endobronchial mass
What microscopic findings are characteristic of squamous cell carcinoma?
- keratinization
- keratin pearls
- dyskeratosis
- intracellular bridges (desmasomes)
What are associated/precursor lesions of squamous cell carcinoma?
- squamous metaplasia
- increasing degrees of squamous dysplasia
- squamous cell carcinoma in-situ (found adjacent to invasive tumor)
What pathology is shown in the provided images?
Squamous cell carcinoma
- Upper middle image
- mass spreading along peri-bronchiolar area
- Bottom right
- classic cavitation
- Bottom middle
- intercellular bridges
- top right
- keratin pearls
What stains are used to diagnose squamous cell carcinoma?
- Positive
- P40
- P63
- Negative
- TTF-1
- Napsin A
What mutation is associated with sqamous cell carcinoma?
highest TP53 mutations of all histologic types
What is large cell carcinoma?
How is it diagnosed?
undifferentiated non-small cell carcinoma that lacks morphologic & immunohistochemical evidence of other differentiated forms of lung cancer
Diagnosis of exclusion
What are the microscopic characteristics of large cell carcinoma?
- micro
- large nuclei
- prominent nucleoli
- moderate amount of cytoplasm
- no pearls, bridges, glands or mucin
What stains are diagnostic for large cell carcinoma?
- Diagnostic - nothin’
- no TTF-1
- no Napsin A
- no p40
- no p63
What lung tumor is shown in the provided image?
large cell carcinoma
large cell with large nuclei & prominent nucleoli
What is the most aggressive lung tumor?
small cell carcinoma
99% of cases occur in smokers
What is the progenitor cell for small cell carcinoma?
What is the staging classification for small cell caricinoma?
- from neuroendocrine progenitor cells
- Staged
- Limited (confined to one side of the thorax & regional nodes)
- Extensive
What are the gross characteristics of small cell carcinoma?
- central or peripheral
- resections not often seen b/c surgery is rarely performed
What are the microscopic characteristics of small cell carcinoma?
- “relatively” small cells
- scant cytoplasm
- nuclear molding (take shape of one adjacent to it)
- finely granular “salt & pepper” chromatin (b/c neuroendocrine)
- inconspicous nucleoli
- lots of mitotic activity
- extensive necrosis
- crush artifact
- azzopardi effect
- spilled chromatin ends up in blood vessels & makes them look blue
What tumor is shown in the provided histological slides?
- Center
- very little cytoplasm
- “salt & pepper” chromatin
- nuclei molding to cell next to it
- Bottom left
- classic necrosis
- Right
- upper right corner: classic necrosis
- azzopardi effect (blue line in middle)
What stains are used to diagnose small cell carcinoma?
What are electron microscopy findings?
- Positive
- Chromogranin (highly specific, low sensitivity)
- Synaptophysin
- +/- TTF-1 (when lung primaries)
- Electron microscopy
- dense core neurosecretory granules
- shown in the provided image?
What type of imaging technique is used in the provided photo & what type of tumor is depicted?
Electron microscopy
small cell carcinoma (neuroendocrine neoplasm)
What type of tumore looks like large cell carcinoma but is positive for chromogranin and has dense core neurosecretory granules in electron microscopy?
large cell neuroendocrine carcinomas
Where do lung cancers most frequently metastasize to?
adrenal glands (image)
liver
brain
bone
What lymph nodes are most commonly involved with lung carcinoma?
bronchial
tracheal
mediastinal
What is the clinical presentation of lung carcinomas?
- Clinical course
- cough, cheest pain, weight loss, dyspnea, hemoptysis, pleural effusion, SVC syndrome
- Horner symdrome
What is Horner Syndrome & what causes it?
- Pancoast tumor (in the apices of the lung)
- direct extension into sympathetic cervical ganglia
- Symptoms
- miosis, ptosis, anhidrosis (no sweating), enophtaimos (eye looks sunken back in head)
- ulnar pain
Cushing syndrome is associated with what type of underlying cancer?
What is its causal mechanism?
- small cell carcinoma of the lung
- Causal Mechanism
- ACTH or ACTH-like substance
Syndrome of Inappropriate antidiuretic hormone secretion is associated with what type of underlying cancer?
What is its causal mechanism?
- Underlying cancer
- Small cell carcinoma
- intracranial neoplasm
- Causal Mechanism
- antidiuretic hormone or atrial natruietic hormone
- hyponatrimia
- hypoosmolality
- increased urine osmolality
- antidiuretic hormone or atrial natruietic hormone
Hypercalcemia is associated with what type of underlying cancer?
What is its causal mechanism?
- Underlying cancer
- squamous cell carcinoma of the lung
- Mechanism
- parathyroid hormone-related protein (PTHRP)
- TGF-alpha
- TNF
- IL-1
What is the treatment for adenocarcinoma that block angiogenesis by inhibiting VEGF?
bevacizumab
What are carcinoid tumors?
Typing features?
they are basically low-grade neuroendocrine
- dense coronary secretory grandules
- positive for chromogranin & synaptophysin
- salt & pepper chromatin
What demographic is most commonly affected by lung carcinoid tumors?
Where are they located within the lung?
Clinical presentation?
Treatment?
- Demographic
- usually <40 yr
- most common pediatric lung tumor
- Location
- central or peripheral
- typically confined to bronchus
- Clinical presentation
- hemoptysis
- infection distal to tumor
- Treatment
- removal usually curative, but atypical are more aggressive
What is the gross appearance of carcinoid tumors of the lung?
- Gross characteristics
- Grey-yellow cut surface
- polypoid
- mucosal covered
- intraluminal masses
What are the characteristic microscopic findings of carcinoid tumors of the lung?
- small uniform cells
- central nuclei
- moderate amount of fine granular cytopllasm (salt & pepper)
- distinct “organoid” architecture
- nests, ribbons, rosette-like arrangements
- prominent fibrovascular stroma
What lung tumor is shown in the provided images?
Carcinoid tumor of the lung
- Upper left
- notice how bright golden-yellow it is
- Upper right
- classic one poking out into the bronchus
- Bottom right
- cells with salt & pepper chromatin
- quite a bit of cytoplasm
- nested growth pattern
How are typical & atypical carcinoid tumors differentiated?
Why does this a matter?
- mitotic activity
- necrosis
- Typical (less mitotic activity & less necrosis) - typically curable
- Atypical (more mitotic activity & more necrosis)
What is a pre-canacer lesion associated with carcinoid tumors?
diffuse neuroendocrine cell hyperplasia
What stains are used to diagnose carcinoid tumors?
What findings would you expect to see with electron microscopy?
- Positive
- Serotonin
- Chromogranin
- Synaptophysin
- +/- TTF-1
- Electron microscopy
- dense core neurosecretory granules
What is a pulmonary hamartoma?
How are they often discovered?
- <3-4 cm benign connective tissue with epithelial clefts
- cartilage most common, cellular fibrous tissue, fat
- ciliated or non-ciliated columnar epithelium (probably not lesional)
incidental “coin lesion” on X-ray
What type of lung tumor is shown in the provided image?
Pulmonary Hamartoma
What is a lymphangiomyomatosis?
What demographic is most commonly affected?
