Lung Cancer Pathology Flashcards

1
Q

Which cells are adenocarcinoma precursors?

A

Clara cells - non-ciliated secretory cells inthe small airways

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2
Q

What are the WHO classes of lung tumors?

A

benign epithelial tumors

malignant epithelial tumors

mesenchymal tumors

lymphoproliferative neoplasms

miscellaneous

metastatic tumors

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3
Q

NSCLC malignant epithelial tumors

A

squamous cell carcinoma

adenocarcinoma

adenosquamous carcinoma

large cell undifferentiated carcinoma

sarcomatoid carcinoma

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4
Q

neuroendocrine neoplasms - malginant epithelial tumors

A

small cell carcinoma

large cell neuroendocrine carcinoma

atypical carcinoid

typical carcinoid

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5
Q

common histologic features of small cell carcinoma

A

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

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6
Q

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

A

synaptophysin, chromogranin, CD56

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7
Q

What molecular markers are associated with lung cancer?

A

activated proto-onco genes

tumor suppressor genes

autocrine growth factors

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8
Q

ras family of oncogenes

A

K-ras

H-ras

N-ras

correlated with cigarette smoking and poor prognosis

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9
Q

EGFR mutations

A

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

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10
Q

benign epithelial tumors

A

papillomas and adenomas

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11
Q

preinvasive tumors

A

squamous dysplasia

atypical adenomatous hyperplasia (AAH)

adenocarcinoma in situ

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12
Q

What is the precursor to small cell carcinoma?

A

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

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13
Q

general histologic features of non-small cell carcinoma

A

tumor cells are large

abundant cytoplasm

vesicular and coarse chromatin

nucleous present

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14
Q

adenocarcinoma

A

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

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15
Q

common patterns of adenocarcinoma

A

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

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16
Q

pathogenesis of adenocarcinoma

A

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

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17
Q

What is the defining feature of atypical adenomatous hyperplasia?

A

cells are less than 5 mm

(type 2 pneumocytes)

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18
Q

lepidic patterning

A

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

suggests EGFR mutation

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19
Q

pemetrexed

A

antifolate to inhibit thymidylate synthase

20
Q

acinar growth patterns

A

seen in adenocarcinomas - formation of glandular structures

suggest K-RAS mutation

21
Q

papillary growth patterns

A

found in adenocarcinoma

tumor filling alveolar space, no fibrovascular coat

more aggressive

suggests K-RAS mutation

22
Q

major adenocarcinoma mutation in smokers vs. non-smokers

A

non-smokers - EGFR

smokers - KRAS

23
Q

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

A

invasion

metastasis

survival

angiogenesis

proliferation

apoptosis

24
Q

KRAS mutation

A

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

25
Q

ALK rearrangements

A

found mostly in solid pattern adenocarcinomas

signet ring cells common

26
Q

squamous cell carcinoma

A

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

27
Q

common histological findings for squamous cell carcinoma

A

keratin production

intercellular bridges

solid growth pattern

tumor necrosis

28
Q

pathophysiologic progression of squamous cell carcinoma

A

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

29
Q

TTF-1

A

common nuclear marker for adenocarcinoma

normally important for development of lung and thyroid

30
Q

p63

A

common nuclear marker for squamous cell carcinoma

important for development of epithelial tissue

31
Q

common features of large cell carcinoma

A

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

32
Q

What are the common patterns of spread for lung tumors?

A

direct extension

dissemination through airways

lymphatic spread

hematogenous spread

pleural seeding

33
Q

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

A

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
34
Q

common clinical findings of carcinoid

A

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

35
Q

common histopathologic findings of carcinoid

A

nesting, palisading, traecular, insular patterns and rosette-like structures

typical <2 mitosis/10 hpf

necrosis

36
Q

atypical carcinoid

A

2-10 mitoses/10 HPF and focal necrosis

37
Q

synaptophysin

A

a neuroendocrine tumor marker

38
Q

What are the major categories of pleural tumors?

A

mesothelial tumors

lymphoproliferative disorders

mesenchymal tumors

mestastatic tumors

39
Q

calretenin

A

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

40
Q

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

A

epithelioid

sarcomatoid

biphasic/mixed

the epithelioid mesotheliomas have much better prognoses

41
Q

solitary fibrous tumors

A

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

42
Q

malignant mesotheliomas

A

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

43
Q

sarcomatoid mesothelioma

A

characterized by spindle shaped cells

44
Q

epithelial mesotheliomas

A

resembles adenocarcinoma

45
Q

biphasic mesothelioma

A

a mix of spindle cells and tumor-forming glands