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Respiratory > Week 3: Lung Cancer > Flashcards

Week 3: Lung Cancer Flashcards

1
Q

Definition of squamous cell carcinoma

A

A malignant epithelial tumor showing keratinization and/or intercellular bridges

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2
Q

Clinical features of squamous cell carcinoma

A
  • makes up 30% of all lung cancers
  • almost all are smokers. Arsenic and HPV is also associated.
  • most tumors arise centrally in main stem, lobar, or segmental bronchi. Slow growing
  • can cause persistent cough, hemoptysis, obstructive pneumonia
  • may cavitate when large
  • tumors tends to remain in thorax, with local metastasis
  • superior sulcus tumors: may invade brachial plexus
  • dx made by exfoliated cells in sputum or bronchial brushing cytology
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3
Q

Gross pathologic features of squamous cell carcinoma

A
  • white or gray, often central masses that involve bronchial wall or protrude into bronchial lumen
  • may be surrounded by yellow-produced by obstructive/cholesterol pneumonia
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4
Q

Histology of squamous cell carcinoma

A
  • requires intercellular bridges and/or keratin formation for diagnosis
  • intercellular bridges are desmosomal junctions between tumor cells
  • keratin occurs as pearls (onion skin looking) or individual cell keratinization
  • immunohistochemistry: most express cytokeratin subset CK5/6 and p63 marker
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5
Q

Pathogenesis of squamous cell carcinoma

A
  1. chronic insult, e.g. cigarette smoke
  2. regeneration of pluripotential basal cells produces squamous metaplasia, leads to dysplasia
  3. then to carcinoma in situ and to invasive squamous cell carcinoma
    - accumulation of genetic abnormalities leads to invasive carcinoma
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6
Q

Small cell carcinoma definition

A

-high grade carcinoma containing characteristic small cells with scant cytoplasm, finely granular nucleoplasm, and absent or minimal nucleoli

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7
Q

Clinical features of small cell carcinoma

A
  • 18-25% of all lung cancers, strongly associated with smoking
  • rapid growing tumor with metastasis at presentation.
  • more common in men
  • Limited Stage: tumor within hemithorax
  • Extensive stage: metastasis outside of hemithorax. Bulky metastasis of mediastinum common.
  • can produce superior vena cava syndrome
  • Paraneoplastic syndrome common: SIADH, Cushings, Eaton-Lambart syndrome
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8
Q

Gross pathology of small cell carcinoma

A
  • occurs in major bronchi and infrequently in periphery of lung
  • may clinically be occult in airways, presenting with bulky mediastinal and extensive lymphangitic metastases
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9
Q

Histology of small cell carcinoma

A
  • round, oval, or spindle shaped cells (Oats)
  • cell size <3 resting lymphocytes
  • cell crowding, with nucleus of one cell indenting that of another
  • granular nucleoplasm, without macro-nucleoli
  • necrosis often present
  • mitotic figures
  • crush artifact: smearing effect of nuclei in bronchial biopsies, makes dx hard
  • immunohistochemistry: 2/3rds express marker. Chromogranin or synaptophysin and all have keratin within tumor cells. TTF-1 present in most cases.
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10
Q

Prognosis and treatment

A
  • poor survival. 3 months for limited stage untreated, 1.5 for extensive
  • surgical resection usually not possible. Treat with chemotherapy and radiation (palliative radiation for extensive stage)
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11
Q

Adenocarcinoma definition

A

-carcinoma with glandular differentiation or mucin production showing acinar, papillary, bronchioloalveolar, or solid growth patterns, or with a mix of these patterns

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12
Q

Clinical features of adenocarcinoma

A

-most common type of lung cancer
-tumors arise from glandular epithelium and usually occur in periphery of lung
-more common in women
-relation to smoking not as high as other lung cancers
-may present with distant metastasis to sites such as brain
-staging important for prognosis
-surgical resection main treatment
5 year survival: 20%

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13
Q

Gross pathology of adenocarcinoma

A
  • tumors usually peripheral, often with puckering of overlying pleura produced by fibrotic retraction
  • cut section: white, gray, show antracotic pigment and gray fibrosis at center
  • often central fibrosis
  • occasional central or endobronchial tumors
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14
Q

Histological patterns of adenocarcinoma

A
  1. Acinar predominant
    - glands and tubules lined by cuboidal or columnar cells, may be mucin-producing or have Clara cells. Always invasive into lung with resulting fibrosis
  2. Papillary predominant:
    - cuboidal to low colunar. Mucinous or non mucinous cells. Growing in stalks and displaying complicated secondary or tertiary branches
  3. Solid predominant:
    - growing in sheets of tumor cells with frequent mucin containing vacuoles
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15
Q

Immunohistochemical findings in adenocarcinomas of lung

A

-TTF-1 (thyroid transcription factor-1): found in most adenocarcinomas of lung origin. Specific for a lung primary

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16
Q

Adenocarcinoma in situ (<3cm) definition

A
  • well differentiated adenocarcinoma, arising in periphery, in which tumor grows upon surface of pre-existing alveolar walls (lepidic growth)
  • no stromal, pleural, or lymphovascular invasion
  • 100% 5 year survival
17
Q

Clinical features of adenocarcinoma in situ

A
  • average presentation in 60s, but can occur in teens and 20s
  • smokers or in Female, Asian, Non-smokers
  • single peripheral nodule less than 3cm
  • needs larger biopsy to make diagnosis since it is defined as non invasive tumor
18
Q

Histology of adenocarcinoma in situ

A
  • 2 subtypes: non-mucinous (most types) and mucinous
  • neoplastic Clara cells and/or Type 2 cells
  • rare mucinous adenocarcinomas in situ consist of tall columnar cells with abundant cytoplasmic mucin
  • Clara cells: columnar with cytoplasmic snouts and eos cytoplasm
  • Type 2 cells: cuboidal with occasional intranuclear eos inclusion
  • both have same outcomes
19
Q

Adenocarcinoma lepidic predominant

A
  • > 3 cm, more likely to invade stroma or lymphovascular structures
  • worse prognosis
  • stromal invasion typically accompanied by desmoplatic reaction as well as cytologic atypia
  • penetration of pleura
  • invasion of lymphatics or vessels or metastasis
20
Q

Large cell carcinoma definition

A
  • undifferentiated non-small cell carcinoma that fails to show squamous or glandular differentiation or extensive mucin secretion
  • dx of exclusion of other types of carcinomas
  • EM: minimal squamous cell or adenocarcinomatous differentiation
21
Q

Clinical features of large cell carcinomas

A
  • symptoms similar to other non small cell carcinomas
  • peripheral tumors
  • same pattern of spread as other small cell carcinomas: lymph nodes, pleura, liver, bone, brain, adrenal, etc
  • outcome depends on stage
22
Q

Pathology of large cell carcinoma

A
  • large peripheral masses
  • diagnosis of exclusion
  • cells grow in sheets, abundant cytoplasm, large lucent nuclei with prominent nucleoli
23
Q

Carcinoid tumor of lung- definition

A
  • A neuroendocrine carcinoma characterized by nests, trabecular, palisading, and ribbon arrangements that suggest at LM level neuroendocrine differentiation
  • tumor cells: uniform cytologic appearance with moderate eosinophilic cytoplasm and punctate nucleoplasm
  • 2 types: typical and atypical
24
Q

Clinical features of carcinoid tumors

A
  • central or peripheral
  • common symptoms assoc. with central tumors: cough, hemoptysis
  • Cushings syndrome due to ectopic ACTH production- uncommon though
  • dx by bronchial biopsy, may have bleeding. Peripheral tumors dx by fine needle aspiration.
  • good overall 5 year survival for typical carcinoids
25
Q

Pathology of carcinoid tumors

A
  • Tumors show nests, trabeculae, etc, suggesting a neuroendocrine tumor. They arise from Kulschitsky cells (like small cell carcinomas).
  • Strong staining for chromogranin, a marker found in dense core (neurosecretory) granules, which are numerous in this tumor.
  • Typical carcinoid: A carcinoid with fewer than 2 mitoses per 10 high-power microscopic fields.
  • Atypical carcinoid: A carcinoid tumor with 2-10 mitoses per 10 high-power microscopic fields or necrosis.
26
Q

Molecular genetics of lung cancer

A
  1. EGFR (epidermal growth factor receptor)
    - expressed in 50% of non-small cell carcinoma of lung (NSCLCs). assoc. with poor prognosis
    - may respond to EGFR tyrosine kinase inhibitors, e.g. gefitinib and erlotinib. Progression free survival
    - assoc. with adenocarcinoma: never smoking Asian women
  2. Ras
    - assoc. with smokers. no drug treatment
  3. ALK (anaplastic lymphoma kinase mutation)
    - encodes a tyrosine kinase receptor
    - assoc. with anaplastic large cell lymphoma t(2;5)(p23;25)
    - signet ring cells, solid tumor growth, younger patients
27
Q

epidemiology of lung cancer

A

2 in incidence and #1 in mortality in both men and women of all cancers

28
Q

Treatment or nonsmall cell lung cancer (NSCLC)

A

Based on stages

  • IA/IB: surgical resection
  • IIA/IIB: surgery+adjuvent chemo
  • IIIA/IIIB: definitive chemo and XRT
  • IV: definitive chemo and palliative XRT
29
Q

how to stage NSCLC tumors: hints

A
  • IA: <3cm
  • IV: end stage metastasis. metastasis outside chest, malignant pleural or pericardial effusion, contralateral lobe satellite noduels
  • IIIA/B: unresectability. N3 contraletral or high nodes. N2 multistation and bulky. Sever invasion.
30
Q

Summary of different lung cancers and associations

A
  1. Squamous cell
    - hypercalcemia from PTHrp excess, AIS
    - cavitate, endobronchial
  2. adenocarcinoma
    - non smokers, EGFR, ALK-4 mutations
    - peripheral, metastatized, copious bronchorrhea
  3. Small cell
    - smokers, central location, extensive mediastinal LAD, metastasized, Paraneoplastic syndrome
31
Q

Paraneoplastic syndromes-mostly associated with SCLC

A
  1. Eaton-Lambert
    - antibiodies to Ca2+ channels
    - proximal muscle weakness, but repetitive movement improves strength because of excess Ca release
  2. Dermatomyositis
    - antibiodies to muscle receptors
    - weakness and skin changes: heliotropic rash, gotran’s papules
  3. Cushings
  4. SIADH
  5. Hypertropic pulmonary Osteoarthropathy (HPO)-ADENOCARCINOMA not SCLC
  6. Gynecomastia-Large breasts from large cell
32
Q

Compression syndromes

A
  1. SVC syndrome-small cell, NHL
    - right sided tumors compress SVC, arm, neck and head swelling
    - grows collaterals
  2. Pancoast tumor syndrome (NSCLC, squamous often)
    - Horner’s syndrome and flushing from nerve compresion
  3. nerve compression syndrome
    - hoarseness from left sided tumors, compress recurrent laryngeal nerve
33
Q

Approach to solitary pulmonary nodules

A

For nodules smaller than 8mm that are solid
-if low risk, follow up by CT based on size
-if high risk: also follow up with CT based on size.
Should be directly resected in operative candidates at high risk for lung cancer.

Respiratory (31 decks)

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