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Snapshot
  • A 69-year-old male with a 50 pack-year smoking history presents to his physician with complaint of worsening cough. He describes frequently coughing up blood in the past few weeks. He has unintentionally lost about 10 pounds of weight in the past month and has felt more fatigued than usual. On physical examination, he has ptosis and a constricted pupil in his left eye. His right eye is normal. A chest radiograph is obtained and is shown in the image.
Introduction
  • Overview lung cancer is a malignancy that affects the lung parenchyma or airways
    • most lung cancers can be divided into
      • small cell lung cancer 
      • non-small cell lung cancer
  • Epidemiology
    • incidence
      • second most common cancer
      • leading cause of cancer-related death
    • risk factors
      • cigarette smoking
        • most important risk factor
        • second-hand smoke exposure is also a risk factor
      • asbestos
      • radon
      • family history of lung cancer
  • 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 either of the following
        • currently smoke
        • has quit smoking within the past 15 years
Classification
 
Small Cell Lung Cancer (SCLC)
Type
Location
Associated Findings
Histology
Small cell (oat cell) lung cancer
  • 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
  • Small dark blue tumor cells with lack of nucleoli and high nuclear:cytoplasm ratio
  • Positive staining 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
  • Central or peripheral
  • Carcinoid syndrome
  • Better prognosis
  • Neuroendocrine cells
  • Chromogranin A positive
 
Presentation
  • Symptoms
    • cough
    • wheezing
    • unintentional weight loss
    • hemoptysis
    • chest pain
    • dyspnea
    • hoarseness
      • suggests involvement of the recurrent laryngeal nerve
  • Physical exam
    • finger clubbing
Imaging
  • Radiography
    • indication
      • initial imaging modality when evaluating a patient with symptoms concerning for lung cancer
        • very important to review previous 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)
      • further evaluate pulmonary nodule found on radiography
        • chest CT should be obtained for all patients with an unclearly characterized solitary pulmonary nodule seen 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
    • solitary pulmonary nodule < 8mm
      • if there are or are not 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
    • differentiating factors
      • abnormal quantiferon or purified protein derivative (PPD) test
      • history of ↑ risk of exposure (e.g., household contact with someone with diagnosed tuberculosis or travel to tuberculosis-endemic area)
Treatment
  • Small cell lung cancer
    • most cases are non-resectable and thus require chemotherapy (e.g., carboplatin and etoposide)
  • Non-small cell lung cancer
    • treatment includes surgical removal, lymph node sampling or dissection, radiation, and chemotherapy
      • depends on the staging
Complications
  • Superior vena cava syndrome
  • Pancoast tumor
    • may cause Horner syndrome
  • Metastasis 
  • Pericardial effusion
  • Pleural effusion
  • Paraneoplastic syndromes
    • hypercalcemia of malignancy
      • ectopic secretion of PTH-related protein (PTHrP)
    • Lambert-Eaton syndrome
    • SIADH
    • Cushing syndrome
 

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Questions (12)
Lab Values
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  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
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
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(M1.ON.13.36) An ill-appearing 70-year-old male smoker presents to your office at 4:00 p.m. The left panel of Figure A shows the patient's appearance when he wakes up in the morning and the right panel shows the patient as he appears after walking around during the day. He complains of dyspnea and cough for several weeks, and on examination you also note his distended neck veins. What is the most likely cause of this patient's illness? Review Topic | Tested Concept

QID: 100839
FIGURES:
1

Congestive heart failure

19%

(29/155)

2

Pancoast tumor (bronchogenic carcinoma)

55%

(86/155)

3

ACE inhibitor therapy

5%

(7/155)

4

Type I hypersensitivity reaction

0%

(0/155)

5

Subclavian steal syndrome

20%

(31/155)

L 2 E

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(M1.ON.13.39) A lung mass of a 50 pack-year smoker is biopsied. If ADH levels were grossly increased, what would most likely be the histologic appearance of this mass? Review Topic | Tested Concept

QID: 100842
1

Tall columnar cells bordering the alveolar septum

2%

(2/94)

2

Sheets of small round cells with hyperchromatic nuclei

79%

(74/94)

3

Layered squamous cells with keratin pearls

7%

(7/94)

4

Hyperplasia of mucin producing glandular tissue

9%

(8/94)

5

Pleomorphic giant cells with leukocyte fragments in cytoplasm

1%

(1/94)

L 2 D

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(M1.ON.13.121) A 55-year-old male smoker presents to your office with hemoptysis, central obesity, and a round face with a "moon-like" appearance. He is found to have a neoplasm near the hilum of his left lung. A biopsy of the tumor reveals small basophilic cells with finely granular nuclear chromatin (a "salt and pepper" pattern). Which of the following is the most appropriate treatment for this patient? Review Topic | Tested Concept

QID: 100924
1

Tamoxifen

2%

(3/142)

2

Prednisone

8%

(11/142)

3

Surgical resection

21%

(30/142)

4

Cisplatin and radiotherapy

67%

(95/142)

5

Watchful waiting

1%

(2/142)

L 3 E

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(M1.ON.13.68) A 54-year-old female is admitted to the hospital for progressive exertional dyspnea and cough productive of tan-colored liquid for 6 months. She has never smoked a day in her life. A lung biopsy is shown in Figure A that demonstrates tall, columnar cells that line the alveoli septa. The most likely diagnosis for this patient is: Review Topic | Tested Concept

QID: 100871
FIGURES:
1

Mesothelioma

0%

(0/23)

2

Squamous cell carcinoma

13%

(3/23)

3

Small cell carcinoma

0%

(0/23)

4

Adenocarcinoma

78%

(18/23)

5

Metastatic breast cancer

9%

(2/23)

L 1 D

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