Lung Cancer Pathology Flashcards
Which cells are adenocarcinoma precursors?
Clara cells - non-ciliated secretory cells inthe small airways
What are the WHO classes of lung tumors?
benign epithelial tumors
malignant epithelial tumors
mesenchymal tumors
lymphoproliferative neoplasms
miscellaneous
metastatic tumors
NSCLC malignant epithelial tumors
squamous cell carcinoma
adenocarcinoma
adenosquamous carcinoma
large cell undifferentiated carcinoma
sarcomatoid carcinoma
neuroendocrine neoplasms - malginant epithelial tumors
small cell carcinoma
large cell neuroendocrine carcinoma
atypical carcinoid
typical carcinoid
common histologic features of small cell carcinoma
small size (generally less than the diameter of 3 small resting lymphocytes)
scant cytoplasm with molding
nuclei is finely granular - salt and pepper appearance
high mitotic rate
frequent necrosis, often in large zones
What stains will any neuro-endocrine tumor be positive for?
synaptophysin, chromogranin, CD56
What molecular markers are associated with lung cancer?
activated proto-onco genes
tumor suppressor genes
autocrine growth factors
ras family of oncogenes
K-ras
H-ras
N-ras
correlated with cigarette smoking and poor prognosis
EGFR mutations
seen in 25% of lung adenocarcinoma, mostly in non-smoking asian women
benign epithelial tumors
papillomas and adenomas
preinvasive tumors
squamous dysplasia
atypical adenomatous hyperplasia (AAH)
adenocarcinoma in situ
What is the precursor to small cell carcinoma?
pluripotent bronchial precursor cell (Stem Cell) or the neuroendocrine cell in the bronchus
general histologic features of non-small cell carcinoma
tumor cells are large
abundant cytoplasm
vesicular and coarse chromatin
nucleous present
adenocarcinoma
a malignant epithelial tumor with glandular differentiation or mucin production, showing acinar, papillary, lepidic, or solid growth patterns or a mixture of these patterns
can occur in non-smokers
more common in women
majority are peripheral in location
common patterns of adenocarcinoma
peripheral adenocarcinoma with desmoplastic fibrosis retracting the overlying pleura
central or endobronchial adenocarcinoma
diffuse pneumonia-like consolidation
diffuse pleural thickening seen in pseudomesotheliomatous carcinoma
adenocarcinoma arising the background of underlying fibrosis
pathogenesis of adenocarcinoma
smoke or somatic mutation → type 2 pneumocyte and clara cell hyperplasia → atypical adenomatous hyperplasia → adenocarcinoma in situe → invasive adenocarcinoma
What is the defining feature of atypical adenomatous hyperplasia?
cells are less than 5 mm
(type 2 pneumocytes)
lepidic patterning
a pattern seen in adenocarcinoma where the tumor cells grow along the alveolar setpa
suggests EGFR mutation
pemetrexed
antifolate to inhibit thymidylate synthase
acinar growth patterns
seen in adenocarcinomas - formation of glandular structures
suggest K-RAS mutation
papillary growth patterns
found in adenocarcinoma
tumor filling alveolar space, no fibrovascular coat
more aggressive
suggests K-RAS mutation
major adenocarcinoma mutation in smokers vs. non-smokers
non-smokers - EGFR
smokers - KRAS
What are the functions of the EGFR receptor in tumor growth?
invasion
metastasis
survival
angiogenesis
proliferation
apoptosis
KRAS mutation
K-RAS involved in signal transduction in MAPK pathway
mutations are downstream of EGFR, so anti-EGFR therapy does not affect K-RAS mutant cancers
ALK rearrangements
found mostly in solid pattern adenocarcinomas
signet ring cells common
squamous cell carcinoma
central in location, involving major bronchi
strongly smoking associated
more likely to experience an elevated calcium level which can result in muscle weakness and cramps
common histological findings for squamous cell carcinoma
keratin production
intercellular bridges
solid growth pattern
tumor necrosis
pathophysiologic progression of squamous cell carcinoma
irritation (from smoke) → squamous metaplasia (bronchial epithelium) → dysplasia → high-grade dysplasia carcinoma in situ (CIS) → invasive SCC
TTF-1
common nuclear marker for adenocarcinoma
normally important for development of lung and thyroid
p63
common nuclear marker for squamous cell carcinoma
important for development of epithelial tissue
common features of large cell carcinoma
diagnosis of exclusion and probably represents either adeno or squamous
cells are large with prominent nucleoli
can have multinucleated tumor cells
central or peripheral in location
What are the common patterns of spread for lung tumors?
direct extension
dissemination through airways
lymphatic spread
hematogenous spread
pleural seeding
What are some of the differences between primary lung tumors vs. metastsis?
primary tumor
- large
- single
- ill defined
- less vascular invasion
- transition
- TTF1+
- CK7+, CK20-
metastatic tumor
- small
- multiple
- well defined
- frequent vascular invasion
- lack of transition
- TTF1-
- variable
common clinical findings of carcinoid
up to half of all bronchopulmonary carcinoids identified as an incidental radiographic finding
most common symptoms are cough and hemoptysis typically relate to bronchial obstruction
Cushing’s syndrome due to ectopic ACTH production
not associated with smoking
arise from neuroendocrine cells
common histopathologic findings of carcinoid
nesting, palisading, traecular, insular patterns and rosette-like structures
typical <2 mitosis/10 hpf
necrosis
atypical carcinoid
2-10 mitoses/10 HPF and focal necrosis
synaptophysin
a neuroendocrine tumor marker
What are the major categories of pleural tumors?
mesothelial tumors
lymphoproliferative disorders
mesenchymal tumors
mestastatic tumors
calretenin
marker fo mesothelial derrived tumors, adenocarcinomas would be negative for this stain
What are the different histologic subtypes and patterns of malignant mesotheliomas?
epithelioid
sarcomatoid
biphasic/mixed
the epithelioid mesotheliomas have much better prognoses
solitary fibrous tumors
benign mesenchymal pleural tumomr (rarely malignant)
arises from submesothelial connective tissue of visceral or parietal pleura
presents as a penduculated circumscribed mass
histology - bland spindle cells in a dense collagenous stroma
malignant mesotheliomas
arises from visceral or parietal pleura
strong association with asbestos exposure
asbestos bodies - asbestos fiber + coating of iron and protein
gross - diffuse lesion that encases the lung
sarcomatoid mesothelioma
characterized by spindle shaped cells
epithelial mesotheliomas
resembles adenocarcinoma
biphasic mesothelioma
a mix of spindle cells and tumor-forming glands
