Lectures 23-24: Lung cancer and pathology Flashcards
Cigarette smokers who have never quit have a ___x risk of lung cancer as compared to non-smokers
20x
About what % of lung cancer cases in females occur in never smokers? Males?
~10%; ~5%
Other risks for lung cancer (7). Which two are fairly important?
Passive tobacco smoke, radiation exposure, air pollution, cooking oil fumes, prior lung disease, FAMILY HISTORY, OCCUPATIONAL EXPOSURE
Genes and lung cancer: gene and risk increase and difficulty
15q24-25 locus (nAChR subunit), 30% increased risk, may be related to smoking addiction itself!
Most common presentation of lung cancer
Pulmonary nodules
T/F: A nodule is asymptomatic; T/F: The majority of nodules are metastatic; T/F: Single pulmonary nodules (SPNs) are common x-ray findings in smokers AND non-smokers
True; False (majority are actually BENIGN); True
How do we deal with pulmonary nodules?
If you’re high risk, all nodules are cancerous until proven otherwise
How can we distinguish a benign vs malignant SPN? (4)
Stability over time, calcification pattern, appearance, metabolic characteristics (tumors tend to take up more glucose on PET)
What are two calcification patterns? What does calcium mean? Suggestive that it’s not cancerous?
Popcorn or central; calcium means it’s been around for a while –> probably not cancerous (CALCIUM GOOD)
What are some other appearances of a potentially cancerous SPN?
Spiculated borer or cavitation BAD
Dx of primary lung cancer (2)
Cytology (from sputum, bronchoscopy, transthoracic needle aspiration), biopsy (needle, bronchscopy, surgery)
Risk of transthoracic needle aspiration
Pneumothorax
Histological categories of lung cancer
Small cell (~15%) and non-small cell (~85%) = squamous cell carcinoma, adenocarcinoma, large cell
Characteristics of small cell lung cancer
Responsive to chemo but common relapses, grows very fast
What is the predominant NSCLC?
Adenocarcinoma
Describe squamous cell tumors
Central, cavitary, strong smoking assocation
Describe adenocarcinomas
Peripheral, most occur in former smokers BUT most common histologic subtype in never smokers; doubling time = about a year
What about adenocarcinoma in situ (Lepidic adenoca) that is difficult?
Lines alveolar spaces like a pneumonia (looks like this)
Characteristics of squamous cell carcinoma and compare doubling tie to adenoca
Bulky, invade adjacent structures, may cavitate; faster doubling time than adenoca
Describe large cell lung cancer (what they look like, prognosis)
Bulky tumors with large cells, poor prognosis
What is a carcinoid tumor? Present with? Common?
Well-differentiated neuroendocrine tumor that arises in central airways; present with wheezing or cough; rare
Describe small cell carcinomas: association, where they arise from, and where they are found
Associated most strongly with smoking; arise from pulmonary neuroendocrine cells; present as central, perihilar masses with associated lymphadenopathy
What does a small cell look like under a microscope?
Large, dark cells with giant nuclei taking up whole cells
What category of syndromes is associated with small cell carcinoma?
Paraneoplastic syndrome because they are made from neuroendocrine tissues
Survival for small cell lung carcinoma; metastases?
5 year, 6.2%; commonly metastasize
When a lung cancer progresses, what does it mean?
Advanced disease –> early cancers are asymptomatic
Lung cancer symptoms (5 categories)
Airway (cough), pleural (chest pain = BAD), mediastinal spread (hoarseness), SVC syndrome, and diaphragm paralysis, distant spread (headache, weakness), others (weight loss, clubbing, paraneoplastic)
Presentation of SVC syndrome
Facial swelling, headache, dyspnea
What kind of lung tumor can present with arm pain? What other syndrome is associated?
Pancoast tumor; Horner’s syndrome
What are two exceptions to the rule that paraneoplastic syndromes are associated with small cell carcinoma?
Hypercalcemia = squamous cell and clubbing = NSCLC
Three typical paraneoplastic syndromes
- Cushing’s syndrome (cortisol production by SCC), 2. SIADH (ADH production by SCC), 3. Eaton-Lambert myasthenic syndrome (autoantibodies to voltage-sensitive calcium channels)
What dx modality is best for central tumors? For peripheral tumors?
Central = bronchoscopy; Peripheral = CT-guided biopsy
T stage
Site, size, local invasion; TX - T4
N stage
Spread to lymph nodes, NX - N3
M stage
Distant metastatic sites, MX - M1b
Staging scale
Stage I - IV
How do we stage non small cell lung cancer?
TMN and staging
How do we stage small cell lung cancer?
Limited = confined to half chest; Extensive = spread beyond half the chest
Is imaging a perfect test for staging?
Nope, you have to do tissue sampling
Stage I
No nodes, no metastaes, no invasion; 65% 5-year survival; tx = resection
Stage II
Ipsilateral peribronchial/hilar nodes or limited invasion; 40% 5-year survival; tx = surgery and chemo +/- radiation
Stage III a and b
Positive ipsilateral mediastinal nodes, greater local invasion; 15% 5-year survival; tx = chemo +/- radiation
Stage IV
Distant metastases or other lung lobe;
Two questions of NSCLC
Is the patient resectable: chance of getting the whole tumor AND Is the patient operable: will the patient survive an operation?
What is the ONLY cure for NSCLC
Surgery
Post-op FEV1 rule of thumb
Rule is to leave with post op FEV1 > 30% or >800 mL
Treatment of small cell lung cancer
Chemotherapy +/- radiation
Describe chemotherapy and radiation therapy for NSCLC
Chemo is life-extending and radiation for local disease control and palliation
Three biomarkers in lung cancer
EGFR (more common in non smokers, respond well to EGFR-TKI); K-Ras mutation (more common in smokers, poor response to TKI and chemo/poor prognosis); EML4-ALK (response to ALK inhibitors)
Lung cancer screening guidelines
Screen with CT for those 55-74 year old smokers, former smokers who quit less than 15 years ago
Precursor lesion for squamous cell carcinoma
Squamous dysplasia and carcinoma in situ
Precursor lesion for adenoarcinoma
Atypical adenomatous hyperplasia
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia can lead to what (non-specific)?
Some carcinoids
5-year survival rate for lung carcinoma
18%
Clinical presentation for lung cancer
Local disease, disseminated disease (bone pain), paraneoplastic syndromes
Lung cancer is often found…
Incidentally
Vast majority of tumors are…
Epithelial (90-95%)
We also see what kind of lung tumor?
Mesothelial
Breakdown epithelial tumor types…(2)
90-95% are carcinomas, 5% are carcinoids (neuroendocrine)
Three NSCLC types. Which is more common?
Squamous, adeno and large cell; adeno (previously squamous)
Small cell carcinoma is what %
20%
Centrally located tumors
Squamous and small cell
Peripherally located tumors
Adeno and large cell
Squamous cell carcinoma: who, presentation
Men, smoking history; sx: central, so bronchial obstruction/atelectasis
What happens to respiratory epithelium before you get squamous cell carcinoma (3 steps)?
Squamous metaplasia –> dysplasia –> carcinoma in situ –> invasive carcinoma; 25% of dysplasia and 50% of Cis get invasive carcinoma
Squamous cell: invasion, neoplasm, gross finding
Locally aggression with late metastasizes; hypercalcemia; cavity in middle due to necrosis
Squamous cell: microscope
Sheets/islands of large polygonal malignant cell with keratinization: keratin pearls or intracellular bridges
Adenocarcinoma: who, mutations
Women, non-smokers; associated with EGFR/EML4-ALK mutations; advances with targeted gene therapy
Who typically has EGFR mutations?
Non-smoking Asian females
Adenocarcinoma: precursor
Atypical adenomatous hyperplasia (AAH) = proliferation of atypical type II pneumoctyes and/or Clara cells lining alveolar walls
How to identify AAH
Pneumocyte proliferation with no surrounding lung problems
What comes after AAH?
Adenocarcinoma in situ = growth of cells entirely along alveolar septa (lepidic growth), greater than 5 mm (bigger than AAH)
Why is the AAH/Ai important classification?
Survival is nearly 100% compared to similar size invasive adenomas
Adenocarcinoma in situ: radiographically; how many nodules?
Called “ground glass,” can have multiple nodules
What happens after Ais? Survival
Minimally invasive adenocarcinoma = 3 cm or less with predominately lepidic pattern and
Most cases of adenos are what kind? Characteristic finding?
Invasive adenocarcinomas = more than 5 mm invasion, characterized by gland formations
Invasive adenocarcinomas: pleural finding
“Pleural puckering” due to pleural invasion
Invasive adenocarcinomas: histologically
Tumor with irregular glands and destruction of lung architecture
Invasive adenocarcinomas: stain
Mucin stain (these produce mucin)
Large cell carcinoma: definition
Undifferentiated malignant epithelial tumor that lacks cytologic features of small cell carcinoma as well as glandular or squamous differentiation; likely squamous or adeno with correct stain
Invasive adenocarcinomas: histologically
Looks like sheets of cells, like undifferencetiated adeno
Small cell carcinoma: who, basic typing, prognosis
Older men, exclusively in cigarette smokers; high grade neuroendocrine carcinoma; very aggressive with early mediastinal lymph node involvement (>5% 5 year survival)
Small cell carcinoma: gross
Central/hilar, white-tan, friable, extensive necrosis
Small cell carcinoma: micro
Small to medium sized dark cells with minimal cytoplasm (high N/C ratio), nuclear modling
Neoplastic syndromes: squamous
PTH hormone activity –> hypercalcemia
Neoplastic syndromes: small cell
ACTH production or ADH production, Eaton-Lambert (like Myasthenia Gravis)
Carcinoid: define, who, presentation
Low grade neuroendocrine carcinoma; young males and females, non-smokers; often a central endobronchial mass leading to obstructive symptoms (cough, hemoptysis, bronchiectasis)
Three neuroendocrine tumors. Common EM finding?
- Carcinoid; 2. Large cell neuroendocrine carcinoma (rare); 3. Small cell; neurosecretory granules (especially in carcinoid)
T/F: Can carcinoid tumors elaborate vasoactive amines?
Yes, sometimes
Carcinoid syndrome
Intermittent attacks of diarrhea, flushing, and cyanosis (usually with metastatic disease)
Carcinoid association
Cushing’s
Carcinoid: gross and histologically
Intraluminal mass with dilation behind it; histologically: uniform, organoid/ball-like pattern with bleeding due to vascularization
Carcinoid: prognosis
Typical = 90%; atypical = 60%
“N” staging based on…
Location of lymph nodes and contralateral involvement
What is the most common site for a metastases from elsewhere?
The lung
How do tumor cells spread to the lung?
Blood or lymph
How do we tell if a lung cancer is metastatic or primary?
Metastatic = multiple lesions
What is superior vena cava syndrome?
Insidious compression of SVC and is LIFE THREATENING = big purple lead
Describe Pancoast tumor
Tumor in apex of the lung and is associated with Horner syndrome and horseness due to recurrent laryngeal nerve disurption
Pleural tumors are typically…
Metastatic
What is a primary pleural tumor?
Malignant mesothelioma
Mesothelioma: who, when
Asbestos exposure (rarely idiopathic and NOT related to smoking), men; develop after long latency period of ~20 years
Mesothelioma: gross
Multiple small nodules that coalesce into confluent “rind”, typically respect pleural boundary and rarely metastasize
Mesothelioma: histological subtypes (3). Why these differences?
Epithelial (round cells), sarcomatoid (spindle cells), Bi-phasic (both morphologies); because it’s not an epithelial cancer, but a mesoderm cancer
Mesothelioma: prognosis
Very poor, most die within 18 months
