[05.29] Lung Tumors

Most frequently diagnosed major cancer in the world

What is the significance of lung cancer globally regarding diagnosis frequency?

Most common cause of cancer mortality worldwide

What is the significance of lung cancer globally regarding mortality?

40 and 70 years

Between what ages does lung cancer occur most often?

50s or 60s

When is the peak incidence of lung cancer?

Tobacco smoking

What is the primary cause of lung cancer due to its carcinogenic effects?

Tobacco smoking, industrial hazards, air pollution, molecular genetics

What four factors are included in the etiology and pathogenesis of lung carcinomas?

80%

What percentage of lung carcinomas occur in active smokers or those who stopped recently?

Amount of daily smoking, tendency to inhale, duration of the smoking habit

What three statistical factors are associated with the frequency of lung cancer?

11%

What percentage of heavy smokers develop lung cancer in their lifetime?

Genetics and secondhand smoke (environmental tobacco smoke)

What two factors, other than tobacco smoking, are involved in the development of lung cancer?

Numerous human carcinogens

What is contained in cigarette smoke for which there is no safe level of exposure?

Cigar and pipe smoking

What smoking habits also increase the risk of developing lung carcinoma?

Squamous metaplasia

What histologic change in the lining epithelium of the respiratory tract is observed in habitual smokers due to irritation?

Pseudostratified columnar ciliated epithelium

What type of epithelium undergoes metaplastic change to squamous epithelium due to cigarette smoking?

Loss of filtration of minute particles

What functional consequence occurs due to the loss of cilia in squamous metaplasia?

Dysplasia

What precursor condition of lung carcinoma is characterized by loss of polarity and disorganized growth?

Loss of polarity, disorganized growth, increased cell size, pleomorphism, hyperchromasia, increased mitosis

What six features characterize dysplastic epithelium?

Carcinoma in situ

What stage follows dysplasia, immediately preceding invasive carcinoma, in the progression of epithelial changes?

Invasive carcinoma

What stage occurs after carcinoma in situ, representing a frank malignancy?

Intensity of exposure to cigarette smoke

What factor has a linear correlation with the appearance of worrisome epithelial changes (dysplastic changes)?

Polycyclic aromatic hydrocarbons (e.g., benzo

a

pyrene)

What carcinogens in cigarette smoke act as initiators?

Phenol derivatives

What carcinogens in cigarette smoke act as promoters?

Polonium-210, carbon-14, and potassium-40

What three radioactive elements are found in cigarette smoke?

High-dose ionizing radiation

What industrial hazard is carcinogenic, associated with increased lung cancer incidence in atomic bomb survivors (e.g., Hiroshima and Nagasaki)?

Uranium

What weakly radioactive substance increases lung cancer rates, particularly in miners?

4x higher

How much higher are lung cancer rates among non-smoking uranium miners compared to the general population?

10x higher

How much higher are lung cancer rates among smoking uranium miners compared to non-smoking uranium miners?

Asbestos

What industrial hazard is associated with lung cancer (most frequent malignancy) and mesothelioma development?

1000x greater

What is the relative increased chance of developing mesothelioma compared to lung cancer in individuals exposed to asbestos?

10 years to 30 years

What is the latent period for the development of lung carcinoma upon exposure to asbestos?

Shorter latent period

What characteristic of lung carcinoma development explains its higher frequency compared to mesothelioma in asbestos exposure?

30 years

What is the latent period for the development of mesothelioma upon exposure to asbestos?

50-90x greater

What is the increased risk of developing lung carcinoma for asbestos workers who smoke (synergistic effect)?

Car brake shoes and clutch pads, building materials (including ceiling and floor tiles), paints, coating, and adhesives, plastics, vermiculite-containing garden products, some talc-containing crayons

What six categories of products/materials may contain asbestos?

Pleural plaques

What common benign sign, often involving the diaphragm, is related to asbestos exposure besides malignancies?

Pleural effusions and parenchymal interstitial fibrosis

What two other benign-associated conditions are related to asbestos exposure aside from malignancies?

Radon

What specific indoor air pollutant is the second leading cause of lung cancer after cigarette smoking?

Genetic alterations

What is the mechanism by which exposures to carcinogens act on lung cells, resulting in a neoplastic phenotype?

c-MYC, KRAS, EGFR, c-MET, c-KIT

What five dominant oncogenes are involved in lung cancer?

p53, RB1, p16(INK4a), multiple loci on chromosome 3p

What four tumor suppressor genes or loci are commonly deleted or inactivated in lung cancer?

c-KIT, MYCN, MYCL, p53, 3p, RB, BCL2

What seven cancer associated genes/loci are involved in small cell lung carcinoma (SCLC)?

EGFR, KRAS, p53, p16(INK4a)

What four cancer associated genes/loci are involved in non-small cell lung carcinoma (NSCLC)?

25%

What percentage of lung cancers worldwide arise in nonsmokers?

Adenocarcinomas

What is the predominant histologic type of lung cancer in nonsmokers and women?

EGFR mutations

What specific mutation do adenocarcinomas in nonsmokers tend to have?

KRAS mutations

What specific mutation do adenocarcinomas in nonsmokers almost never have?

Adenocarcinoma (50%)

What is the most common major histologic category of lung carcinoma?

Squamous cell carcinoma (20%)

What is the second most common major histologic category of lung carcinoma?

Small cell carcinoma (15%)

What is the third most common major histologic category of lung carcinoma?

Large cell carcinoma (2%)

What is the least common major histologic category of lung carcinoma?

Squamous cell and small cell carcinoma

What two histologic types of lung carcinoma have the strongest relationship to smoking?

SSS (Small Cell Carcinoma, Squamous Cell Carcinoma, Smoking)

What mnemonic is associated with carcinomas linked to smoking?

Always

How frequently does Small Cell Carcinoma metastasize?

High initial response

What is the response of Small Cell Carcinoma to chemotherapy?

Less

How frequently does Non-small Cell Carcinoma metastasize?

Less responsive

What is the response of Non-small Cell Carcinoma to chemotherapy?

Surgical resection (e.g., lobectomy)

What treatment is Non-small Cell Carcinoma amenable to, despite its low response to chemotherapy?

Chemotherapy

What treatment are patients with Small Cell Carcinoma subject to due to its poor prognosis and ability to metastasize?

Non-small cell carcinoma

What broader classification may be used by a pathologist when they cannot commit to a specific histologic type (e.g., adenocarcinoma, squamous cell, large cell carcinoma)?

Immunohistochemical stain

What diagnostic step is suggested for a more specific diagnosis when a broader classification is used?

Thyroid Transcription Factor-1 (TTF1)

What stain is specific for adenocarcinoma of lung origin?

Hilus of the lung (central)

Where do lung carcinomas, such as squamous cell carcinoma, arise most often?

Periphery (from alveolar septal cells or terminal bronchioles)

Where is the increasing number of primary carcinomas, predominantly adenocarcinomas, arising?

Adrenals (50%), liver (30-50%), brain (20%), bone (20%)

What are the four favored distant sites of metastases?

Malignant epithelial tumors with glandular differentiation or mucin production by tumor cells

What is the definition of Adenocarcinoma?

Glandular differentiation or mucin production

What two features are the clues to diagnose adenocarcinoma?

Well-differentiated adenocarcinoma

What grade of adenocarcinoma forms obvious glands or acini?

Poorly differentiated adenocarcinoma

What grade of adenocarcinoma features acinar formation that is very rare, presenting as sheets of malignant cells?

Moderately differentiated adenocarcinoma

What grade of adenocarcinoma features both glands and solid areas?

Women and nonsmokers

What two demographics is adenocarcinoma the most common type of lung cancer in?

Slower

How does the growth rate of Adenocarcinoma compare to Squamous Cell Carcinoma?

Earlier and widely

How does Adenocarcinoma metastasize compared to Squamous Cell Carcinoma?

EGFR gene

What gene, when mutated or amplified, characterizes Adenocarcinomas in women, nonsmokers, and those of Asian origin, showing improved survival with inhibitors?

Tyrosine kinase inhibitors

What class of drugs are tumors with EGFR mutations responsive to?

KRAS mutations

What specific mutation highly correlates with worse outcome and resistance to EGFR inhibitors in Adenocarcinoma?

Atypical adenomatous hyperplasia

What is the first precursor lesion in the summary steps for Adenocarcinoma?

Adenocarcinoma in situ (formerly called bronchoalveolar carcinoma)

What precursor lesion follows atypical adenomatous hyperplasia?

Minimally invasive/microinvasive adenocarcinoma

What stage follows adenocarcinoma in situ?

Invasive adenocarcinoma (invasive component > 5mm)

What final invasive stage follows minimally invasive adenocarcinoma?

Peripherally located, rather than hilar

What is the typical location of Adenocarcinoma grossly?

Smaller

What is the size of Adenocarcinoma compared to Squamous Cell Carcinoma?

Tan-green to tan-white, creamish

What is the typical color of Adenocarcinoma grossly?

Loss of polarity, increase in the size of nuclei, hyperchromasia, a lot of mitosis

What four malignant features characterize the lining epithelial cells of Adenocarcinoma?

Nuclear-cytoplasmic ratio becomes 1:1

What happens to the nuclear-cytoplasmic ratio in malignant lining epithelial cells of Adenocarcinoma?

If positive, nuclei would stain brown

What characteristic indicates TTF-I positivity in adenocarcinoma?

Lepidic-predominant, acinar-predominant, papillary-predominant, solid-predominant with mucin production

What are the four predominant histological subtypes of Adenocarcinoma?

Lepidic-predominant adenocarcinoma

What subtype exhibits cells proliferating along the surface of intact alveolar walls without stromal invasion?

Acinar-predominant adenocarcinoma

What subtype exhibits the presence of obvious glands or tubule formation?

Papillary-predominant adenocarcinoma

What subtype exhibits finger-like projections with a central fibrovascular core?

Solid-predominant adenocarcinoma with mucin production

What subtype exhibits solid sheets of malignant cells with indistinct papilla, indicative of poor differentiation?

≤ 5mm

What is the maximum size of Atypical Adenomatous Hyperplasia?

≤ 3 cm

What is the maximum size of Adenocarcinoma in situ?

Dysplastic pneumocytes lining alveolar walls that are mildly fibrotic

What characterizes Atypical Adenomatous Hyperplasia histologically?

Cuboidal epithelium

What type of epithelium lines the alveolar walls in atypical adenomatous hyperplasia?

No penetration of the basement membrane

What feature is characteristic of In situ carcinomas, including Adenocarcinoma in situ?

Composed entirely of dysplastic cells growing along preexisting alveolar septae

What is the description of Adenocarcinoma in situ lesions (≤ 3 cm)?

Cuboidal to columnar cells, with enlarged hyperchromatic nuclei

What characterizes the dysplastic pneumocytes in Adenocarcinoma in situ?

≤ 5mm or ≤ 0.5 cm

What is the maximum size of the invasive component in Minimally Invasive/Microinvasive Adenocarcinoma (≤ 3cm)?

Better prognosis

What is the prognosis of Minimally Invasive/Microinvasive Adenocarcinoma compared to invasive carcinomas of the same size?