Lung Cancer Pathology

Question 1

Which cells are adenocarcinoma precursors?

Answer 1

Clara cells - non-ciliated secretory cells inthe small airways

Question 2

What are the WHO classes of lung tumors?

Answer 2

benign epithelial tumors

malignant epithelial tumors

mesenchymal tumors

lymphoproliferative neoplasms

miscellaneous

metastatic tumors

Question 3

NSCLC malignant epithelial tumors

Answer 3

squamous cell carcinoma

adenocarcinoma

adenosquamous carcinoma

large cell undifferentiated carcinoma

sarcomatoid carcinoma

Question 4

neuroendocrine neoplasms - malginant epithelial tumors

Answer 4

small cell carcinoma

large cell neuroendocrine carcinoma

atypical carcinoid

typical carcinoid

Question 5

common histologic features of small cell carcinoma

Answer 5

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

Question 6

What stains will any neuro-endocrine tumor be positive for?

Answer 6

synaptophysin, chromogranin, CD56

Question 7

What molecular markers are associated with lung cancer?

Answer 7

activated proto-onco genes

tumor suppressor genes

autocrine growth factors

Question 8

ras family of oncogenes

Answer 8

K-ras

H-ras

N-ras

correlated with cigarette smoking and poor prognosis

Question 9

EGFR mutations

Answer 9

seen in 25% of lung adenocarcinoma, mostly in non-smoking asian women

Question 10

benign epithelial tumors

Answer 10

papillomas and adenomas

Question 11

preinvasive tumors

Answer 11

squamous dysplasia

atypical adenomatous hyperplasia (AAH)

adenocarcinoma in situ

Question 12

What is the precursor to small cell carcinoma?

Answer 12

pluripotent bronchial precursor cell (Stem Cell) or the neuroendocrine cell in the bronchus

Question 13

general histologic features of non-small cell carcinoma

Answer 13

tumor cells are large

abundant cytoplasm

vesicular and coarse chromatin

nucleous present

Question 14

adenocarcinoma

Answer 14

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

Question 15

common patterns of adenocarcinoma

Answer 15

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

Question 16

pathogenesis of adenocarcinoma

Answer 16

smoke or somatic mutation → type 2 pneumocyte and clara cell hyperplasia → atypical adenomatous hyperplasia → adenocarcinoma in situe → invasive adenocarcinoma

Question 17

What is the defining feature of atypical adenomatous hyperplasia?

Answer 17

cells are less than 5 mm

(type 2 pneumocytes)

Question 18

lepidic patterning

Answer 18

a pattern seen in adenocarcinoma where the tumor cells grow along the alveolar setpa

suggests EGFR mutation

Question 19

pemetrexed

Answer 19

antifolate to inhibit thymidylate synthase

Question 20

acinar growth patterns

Answer 20

seen in adenocarcinomas - formation of glandular structures

suggest K-RAS mutation

Question 21

papillary growth patterns

Answer 21

found in adenocarcinoma

tumor filling alveolar space, no fibrovascular coat

more aggressive

suggests K-RAS mutation

Question 22

major adenocarcinoma mutation in smokers vs. non-smokers

Answer 22

non-smokers - EGFR

smokers - KRAS

Question 23

What are the functions of the EGFR receptor in tumor growth?

Answer 23

invasion

metastasis

survival

angiogenesis

proliferation

apoptosis

Question 24

KRAS mutation

Answer 24

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

Question 25

ALK rearrangements

Answer 25

found mostly in solid pattern adenocarcinomas signet ring cells common

Question 26

squamous cell carcinoma

Answer 26

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

Question 27

common histological findings for squamous cell carcinoma

Answer 27

keratin production intercellular bridges solid growth pattern tumor necrosis

Question 28

pathophysiologic progression of squamous cell carcinoma

Answer 28

irritation (from smoke) → squamous metaplasia (bronchial epithelium) → dysplasia → high-grade dysplasia carcinoma in situ (CIS) → invasive SCC

Question 29

TTF-1

Answer 29

common nuclear marker for adenocarcinoma normally important for development of lung and thyroid

Question 30

p63

Answer 30

common nuclear marker for squamous cell carcinoma important for development of epithelial tissue

Question 31

common features of large cell carcinoma

Answer 31

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

Question 32

What are the common patterns of spread for lung tumors?

Answer 32

direct extension dissemination through airways lymphatic spread hematogenous spread pleural seeding

Question 33

What are some of the differences between primary lung tumors vs. metastsis?

Answer 33

**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

Question 34

common clinical findings of carcinoid

Answer 34

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

Question 35

common histopathologic findings of carcinoid

Answer 35

nesting, palisading, traecular, insular patterns and rosette-like structures typical \<2 mitosis/10 hpf necrosis

Question 36

atypical carcinoid

Answer 36

2-10 mitoses/10 HPF and focal necrosis

Question 37

synaptophysin

Answer 37

a neuroendocrine tumor marker

Question 38

What are the major categories of pleural tumors?

Answer 38

mesothelial tumors lymphoproliferative disorders mesenchymal tumors mestastatic tumors

Question 39

calretenin

Answer 39

marker fo mesothelial derrived tumors, adenocarcinomas would be negative for this stain

Question 40

What are the different histologic subtypes and patterns of malignant mesotheliomas?

Answer 40

epithelioid sarcomatoid biphasic/mixed the epithelioid mesotheliomas have much better prognoses

Question 41

solitary fibrous tumors

Answer 41

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

Question 42

malignant mesotheliomas

Answer 42

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

Question 43

sarcomatoid mesothelioma

Answer 43

characterized by spindle shaped cells

Question 44

epithelial mesotheliomas

Answer 44

resembles adenocarcinoma

Question 45

biphasic mesothelioma

Answer 45

a mix of spindle cells and tumor-forming glands