Lung Cancer

Snap Shot

A 69-year-old male with a 50-pack-year smoking history presents with worsening cough, weight loss, and repeated episodes of hemoptysis. A chest radiograph is taken and shown at right.

Overview

Lung cancer is the leading cause of malignancy-related mortality
There are several types of lung cancer (ordered from most to least common)
- adenocarcinoma
- squamous cell carcinoma
- small cell carcinoma
- large cell carcinoma
- carcinoid tumor
- mesothelioma
Epidemiology
- highest incidence between 5th and 6th decade
- rates are increasing in women and declining in men
- risk factors are type specific (see below)
Presentation
- symptoms
  - cough
  - dyspnea
  - hemoptysis
- physical exam
  - bronchial obstruction
  - wheezing
  - weight loss
Evaluation
- imaging
  - chest radiograph
    - "coin" lesion
    - important to compare to previous films if available
  - CT
- sputum cytology
- fine-needle aspiration (FNA)
- bronchoscopy +/- lavage
Differential diagnosis
- hamartomas
- granulomatous disease
  - e.g. histoplasmosis and tuberculosis
Complications
- superior vena cava syndrome
- paraneoplastic syndromes
- hoarseness (recurrent laryngeal nerve involvement)
- pleural or pericardial effusions
- Pancoast tumor
  - Horner syndrome

Squamous Cell Carcinoma

Introduction
- strong link to smoking
- more common in men
Presentation
- central (hilar) cavitating lesion
- can ectopically secrete PTH-related protein (PTHrP)
  - results in parathyroid-like hypercalcemia and hypophosphatemia
Histology
- keratin pearls and intercellular bridges
- may stain with Pap stain (as with squamous cell carcinoma of the cervix)
Treatment
- surgical resection
  - indications
    - if early stage
- chemotherapy and/or radiation
  - indications
    - late stage

Adenocarcinoma

Introduction
- there are two subtypes
  - bronchial
    - most common lung cancer in non-smokers and females
    - can develop in site of prior inflammation or injury
    - cancer of neuroendocrine origin
    - no association with smoking
  - bronchioalveolar
    - cancer of Clara cells, mucin-secreting cells, or type II pneumocytes
    - most cases have an association with smoking
Presentation
- peripheral lesions
- bronchial
  - most commonly presents with hemoptysis
- bronchioalveolar
  - can present like pneumonia
    - consolidation on chest radiograph and copious sputum production
  - can result in hypertrophic osteoarthropathy
Histology
- bronchial
  - varies
- bronchioalveolar
  - growth along preexisting structures
  - destruction of alveolar architecture or invasion
Treatment
- surgical resection
  - indications
    - if early stage
- chemotherapy and/or radiation
  - indications
    - late stage

Small Cell Carcinoma

Introduction
- more common in men
- strong association with smoking
- very aggressive
Presentation
- central lesions
- associations
  - ectopic production of ACTH or ADH
  - Lambert-Eaton syndrome
Histology
- stain positive for enolase, chromogranin, and synaptophysin
  - neuroendocrine markers
- Kulchitsky cells
  - small, dark blue cells
- undifferentiated appearance
Treatment
- chemotherapy and/or radiation
  - indications
    - nearly all are metastatic prior to diagnosis and therefore inoperable

Large Cell Carcinoma

Introduction
- strong relationship to smoking
- poor prognosis
Presentation
- peripheral or central lesion
- associated with gynecomastia and galactorrhea
Histology
- pleomorphic giant cells
- very anaplastic
Treatment
- surgical resection
  - indications
    - preferred modality
- chemotherapy and radiation
  - indications
    - are less effective and used less often

Carcinoid Tumor

Introduction
- more common in the GI tract but may arise in the lung (endobronchial)
Presentation
- can cause carcinoid syndrome
  - flushing, diarrhea, wheezing, and salivation

Mesothelioma

Introduction
- cancer of the pleura
- associated with asbestosis
Presentation
- hemorrhagic pleural effusions
Histology
- psammoma bodies
Diagnosis
- imaging
  - shows pleural thickening
- electron microscopy
  - gold standard
  - shows cells with large number of long, slender microvilli
  - tonofilaments also present
Treatment
- surgery
  - indications
    - early stage and lesion is localized
- radiation and/or chemotherapy
  - indications
    - if lesion is diffuse/metastatic

Metastases

Introduction
- primary cancers are most commonly
  - breast
  - colon
  - kidney
Presentation
- most commonly presents with dyspnea

Lung Cancer Overview

Lung Cancer Explained Clearly

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