Week 3: Lung Cancer Flashcards
Definition of squamous cell carcinoma
A malignant epithelial tumor showing keratinization and/or intercellular bridges
Clinical features of squamous cell carcinoma
- 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
Gross pathologic features of squamous cell carcinoma
- 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
Histology of squamous cell carcinoma
- 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
Pathogenesis of squamous cell carcinoma
- chronic insult, e.g. cigarette smoke
- regeneration of pluripotential basal cells produces squamous metaplasia, leads to dysplasia
- then to carcinoma in situ and to invasive squamous cell carcinoma
- accumulation of genetic abnormalities leads to invasive carcinoma
Small cell carcinoma definition
-high grade carcinoma containing characteristic small cells with scant cytoplasm, finely granular nucleoplasm, and absent or minimal nucleoli
Clinical features of small cell carcinoma
- 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
Gross pathology of small cell carcinoma
- occurs in major bronchi and infrequently in periphery of lung
- may clinically be occult in airways, presenting with bulky mediastinal and extensive lymphangitic metastases
Histology of small cell carcinoma
- 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.
Prognosis and treatment
- 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)
Adenocarcinoma definition
-carcinoma with glandular differentiation or mucin production showing acinar, papillary, bronchioloalveolar, or solid growth patterns, or with a mix of these patterns
Clinical features of adenocarcinoma
-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%
Gross pathology of adenocarcinoma
- 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
Histological patterns of adenocarcinoma
- 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 - Papillary predominant:
- cuboidal to low colunar. Mucinous or non mucinous cells. Growing in stalks and displaying complicated secondary or tertiary branches - Solid predominant:
- growing in sheets of tumor cells with frequent mucin containing vacuoles
Immunohistochemical findings in adenocarcinomas of lung
-TTF-1 (thyroid transcription factor-1): found in most adenocarcinomas of lung origin. Specific for a lung primary
Adenocarcinoma in situ (<3cm) definition
- 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
Clinical features of adenocarcinoma in situ
- 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
Histology of adenocarcinoma in situ
- 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
Adenocarcinoma lepidic predominant
- > 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
Large cell carcinoma definition
- 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
Clinical features of large cell carcinomas
- 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
Pathology of large cell carcinoma
- large peripheral masses
- diagnosis of exclusion
- cells grow in sheets, abundant cytoplasm, large lucent nuclei with prominent nucleoli
Carcinoid tumor of lung- definition
- 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
Clinical features of carcinoid tumors
- 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
Pathology of carcinoid tumors
- 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.
Molecular genetics of lung cancer
- 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 - Ras
- assoc. with smokers. no drug treatment - 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
epidemiology of lung cancer
2 in incidence and #1 in mortality in both men and women of all cancers
Treatment or nonsmall cell lung cancer (NSCLC)
Based on stages
- IA/IB: surgical resection
- IIA/IIB: surgery+adjuvent chemo
- IIIA/IIIB: definitive chemo and XRT
- IV: definitive chemo and palliative XRT
how to stage NSCLC tumors: hints
- 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.
Summary of different lung cancers and associations
- Squamous cell
- hypercalcemia from PTHrp excess, AIS
- cavitate, endobronchial - adenocarcinoma
- non smokers, EGFR, ALK-4 mutations
- peripheral, metastatized, copious bronchorrhea - Small cell
- smokers, central location, extensive mediastinal LAD, metastasized, Paraneoplastic syndrome
Paraneoplastic syndromes-mostly associated with SCLC
- Eaton-Lambert
- antibiodies to Ca2+ channels
- proximal muscle weakness, but repetitive movement improves strength because of excess Ca release - Dermatomyositis
- antibiodies to muscle receptors
- weakness and skin changes: heliotropic rash, gotran’s papules - Cushings
- SIADH
- Hypertropic pulmonary Osteoarthropathy (HPO)-ADENOCARCINOMA not SCLC
- Gynecomastia-Large breasts from large cell
Compression syndromes
- SVC syndrome-small cell, NHL
- right sided tumors compress SVC, arm, neck and head swelling
- grows collaterals - Pancoast tumor syndrome (NSCLC, squamous often)
- Horner’s syndrome and flushing from nerve compresion - nerve compression syndrome
- hoarseness from left sided tumors, compress recurrent laryngeal nerve
Approach to solitary pulmonary nodules
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.
