Lung Cancer - Oncology - Medbullets Step 2/3

Snapshot

A 65-year-old man with a 40 pack-year smoking history presents to his primary care physician for fatigue and cough. He reports that his symptoms began approximately 1 year ago and has progressively worsened. He has noticed a streak of blood when coughing into a napkin. He says that at times he wakes up from sleep drenched in sweat. Compared to his last visit 4 months ago he has lost 12 pounds which he states is unintentional. Physical examination is notable for finger clubbing. Radiography of the chest demonstrates a pulmonary nodule, and no prior imaging is available. A CT scan of the chest demonstrates an 11 mm pulmonary eccentric nodule located peripherally.

Introduction

Clinical definition
- malignancy that affects the lung parenchyma or airways
  - most lung cancers can be divided into
    - small cell lung cancer
    - non-SCLC

Small Cell Lung Cancer (SCLC)
Type	Location	Associated Findings	Histology
SCLC (oat cell)	Central	MYC gene amplication May produce adrenocorticotropic hormone (ACTH) leads to Cushing syndrome excessive anti-diuretic hormone (ADH) leads to syndrome of inappropriate ADH (SIADH) presynaptic calcium channel antibodies leads to Lambert Eaton syndrome	Kulchitsky cells Positive for neuron-specific enolase chromogranin A

Non-Small Cell Lung Cancer (NSCLC)
Type	Location	Associated Findings	Histology
Adenocarcinoma	Peripheral	Most common cause of lung cancer in non-smokers cause of lung cancer (excluding metastasis) Adenocarcinoma in situ tumor growth along alveolar structures lepidic growth pattern Patients may have hypertrophic osteoarthropathy Common gene mutations include KRAS EGFR ALK	Typically mucin positive and has a glandular appearance
Large cell carcinoma	Peripheral	Associated with a poor prognosis Highly associated with smoking	Pleomorphic giant cells
Squamous cell carcinoma of the lung	Central	Can arise from the bronchus	Keratin pearls Intracellular bridges
Bronchial carcinoid tumor	-	Carcinoid syndrome Better prognosis	Neuroendocrine cells Chromogranin A positive

Epidemiology
- incidence
  - second most common cancer
  - leading cause of cancer-related death
- risk factors
  - cigarette smoking
    - most important risk factor
    - second-hand smoking
  - asbestos
  - radon
Etiology
- tobacco smoke is the most common cause
Prognosis
- depends on cancer type and severity
Screening
- performed with a low-dose computerized tomography (CT) scan of the chest
  - indicated in patients 55-80 years of age who have a 30 pack-year smoking history and
    - currently smoke or
    - has quit within the past 15 years

Presentation

Symptoms
- cough
- unintentional weight loss
- hemoptysis
- chest pain
- dyspnea
- hoarseness
  - suggests involvement in the recurrent laryngeal nerve

Imaging

Radiography
- indication
  - initial imaging modality when evaluating a patient with symptoms concerning for lung cancer
    - it is highly important to review old chest imaging to assess for lesion properties and changes
Computerized tomography (CT) scan
- indication
  - perform with low-doses to screen for lung cancer (review "screening" in the introduction)
  - to further evaluate pulmonary nodule found on radiography

Studies

Laboratory testing
- complete blood count
- liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, and total bilirubin)
  - abnormalities may suggest liver metastasis
- alkaline phosphatase
  - abnormalities may suggest liver or bone metastasis
    - a gamma-glutamyl transpeptidase (GGT) should be obtained to differentiate between liver or bone involvement
- calcium
  - abnormalities may suggest bone metastasis or paraneoplastic syndromes
Pulmonary function tests
Evaluation of an incidental solitary pulmonary nodule
- introduction
  - benign features
    - diffuse
    - central
    - popcorn
    - concentric
  - malignant features
    - ground-glass
    - eccentric
- chest CT should be obtained for all patients with an unclearly characterized solitary pulmonary nodule seen on radiography
- solitary pulmonary nodule < 8mm
  - if there are or aren't risk factors, one typically does surveillance with a chest CT in a few months depending on the size of the lesion
- solitary pulmonary nodule > 8mm
  - very low probability of malignancy
    - CT surveillance
  - low/moderate probability of malignancy
    - positron emission tomography (PET) scan
      - if absent or mild uptake
        
        CT surveillance
      - if moderate or intense uptake
        
        biopsy or video-assisted thoracoscopic surgery
  - high probability of malignancy
    - staging evaluation with or without PET scan

Differential

Tuberculosis (Tb)
- differentiating factors
  - abnormal quantiferon or purified protein derivative (PPD) test
  - history of increased risk of exposure (e.g., household contact with someone with diagnosed Tb and travel to Tb endemic area)

Treatment

SCLC
- most cases are non-resectable and thus require chemotherapy (e.g., carboplatin and etoposide)
NSCLC
- treatment includes surgical removal, lymph node sampling or dissection, radiation, and chemotherapy
  - depends on the staging

Complications

Superior vena cava syndrome
Pancoast tumor
Metastasis
Horner syndrome
Pericardial effusion
Pleural effusion
Paraneoplastic syndromes
- Lambert-Eaton syndrome
- SIADH
- Cushing syndrome

Blood, Plasma, Serum	Reference Range
ALT	8-20 U/L
Amylase, serum	25-125 U/L
AST	8-20 U/L
Bilirubin, serum (adult) Total // Direct	0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca²⁺)	8.4-10.2 mg/dL
Cholesterol, serum	Rec: < 200 mg/dL
Cortisol, serum	0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h
Creatine kinase, serum	Male: 25-90 U/L Female: 10-70 U/L
Creatinine, serum	0.6-1.2 mg/dL
Electrolytes, serum
Sodium (Na⁺)	136-145 mEq/L
Chloride (Cl^-)	95-105 mEq/L
Potassium (K⁺)	3.5-5.0 mEq/L
Bicarbonate (HCO₃^-)	22-28 mEq/L
Magnesium (Mg²⁺)	1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)
24-28 wks // 32-36 wks	30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks	40-220 ng/mL // 80-350 ng/mL
Ferritin, serum	Male: 15-200 ng/mL Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma	Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250
pH	7.35-7.45
PCO₂	33-45 mmHg
PO₂	75-105 mmHg
Glucose, serum	Fasting: 70-110 mg/dL 2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation	Fasting: <5 ng/mL Provocative stimuli: > 7ng/mL
Immunoglobulins, serum
IgA	76-390 mg/dL
IgE	0-380 IU/mL
IgG	650-1500 mg/dL
IgM	40-345 mg/dL
Iron	50-170 μg/dL
Lactate dehydrogenase, serum	45-90 U/L
Luteinizing hormone, serum/plasma	Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL
Osmolality, serum	275-295 mOsmol/kd H₂O
Parathyroid hormone, serume, N-terminal	230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C)	20-70 U/L
Phosphorus (inorganic), serum	3.0-4.5 mg/dL
Prolactin, serum (hPRL)	< 20 ng/mL
Proteins, serum

Hematologic	Reference Range
Bleeding time	2-7 minutes
Erythrocyte count	Male: 4.3-5.9 million/mm³ Female: 3.5-5.5 million mm³
Erythrocyte sedimentation rate (Westergren)	Male: 0-15 mm/h Female: 0-20 mm/h
Hematocrit	Male: 41%-53% Female: 36%-46%
Hemoglobin A1c	≤ 6 %
Hemoglobin, blood	Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL
Hemoglobin, plasma	1-4 mg/dL
Leukocyte count and differential
Leukocyte count	4,500-11,000/mm³
Segmented neutrophils	54%-62%
Bands	3%-5%
Eosinophils	1%-3%
Basophils	0%-0.75%
Lymphocytes	25%-33%
Monocytes	3%-7%
Mean corpuscular hemoglobin	25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration	31%-36% Hb/cell
Mean corpuscular volume	80-100 μm³
Partial thromboplastin time (activated)	25-40 seconds
Platelet count	150,000-400,000/mm³
Prothrombin time	11-15 seconds
Reticulocyte count	0.5%-1.5% of red cells
Thrombin time	< 2 seconds deviation from control
Volume
Plasma	Male: 25-43 mL/kg Female: 28-45 mL/kg
Red cell	Male: 20-36 mL/kg Female: 19-31 mL/kg

Cerebrospinal Fluid	Reference Range
Cell count	0-5/mm³
Chloride	118-132 mEq/L
Gamma globulin	3%-12% total proteins
Glucose	40-70 mg/dL
Pressure	70-180 mm H₂O
Proteins, total	< 40 mg/dL

Sweat	Reference Range
Chloride	0-35 mmol/L
Urine
Calcium	100-300 mg/24 h
Chloride	Varies with intake
Creatinine clearance	Male: 97-137 mL/min Female: 88-128 mL/min
Estriol, total (in pregnancy)
30 wks	6-18 mg/24 h
35 wks	9-28 mg/24 h
40 wks	13-42 mg/24 h
17-Hydroxycorticosteroids	Male: 3.0-10.0 mg/24 h Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total	Male: 8-20 mg/24 h Female: 6-15 mg/24 h
Osmolality	50-1400 mOsmol/kg H₂O
Oxalate	8-40 μg/mL
Potassium	Varies with diet
Proteins, total	< 150 mg/24 h
Sodium	Varies with diet
Uric acid	Varies with diet
Body Mass Index (BMI)	Adult: 19-25 kg/m²