Small cell lung cancer (SCLC), previously known as oat cell carcinoma, is considered distinct from other lung cancers, which are called non–small cell lung cancers (NSCLCs), on the basis of their clinical and biologic characteristics. This high-power field photomicrograph, stained with hematoxylin and eosin (H&E), displays SCLC on the left side, with normal respiratory epithelium on the right side.

Which of the following statements about SCLC is not true?

1. SCLC is a malignant epithelial tumor consisting of small cells with scant cytoplasm that are round, oval, or spindle-shaped
2. On histology, SCLC has the appearance of a poorly differentiated tumor that is categorized as high-grade neuroendocrine carcinoma
3. On autopsy of a SCLC patient, coexisting SCLC and NSCLC may be noted
4. Small cell carcinomas originate only in the lung

Image courtesy of Medscape.

Answer: D. Small cell carcinomas originate only in the lung.

Although the majority (~95%) of SCLCs do originate in the lungs, the remainder can arise from extrapulmonary structures, such as the nasopharynx, the gastrointestinal (GI) tract, and the genitourinary (GU) tract. Lung cancer can originate in the bronchi, bronchioles, and alveoli (shown).

Image courtesy of American Cancer Society.

This chest x-ray shows a large tumor in the left upper lobe (red arrow).

Image courtesy of Wikimedia Commons.

A substantial increase in US cigarette consumption in the first half of the 20th century led to a corresponding increase in deaths from lung cancer after a lag time in the range of 20 years. The graph in this slide illustrates the increase in cigarette consumption in the United States (expressed in terms of cigarettes smoked per person per year) and the associated rise in lung cancer mortality (expressed in terms of deaths per 100,000 people) from the 1900s into the 1970s.

Image courtesy of Wikimedia Commons.

For SCLC as well as NSCLC, clinical staging according to the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system is helpful in estimating the prognosis.^[1]

For full staging of SCLC, which of the following is/are not necessary?

1. Serum alkaline phosphatase (ALP) level
2. Complete blood count (CBC), serum electrolyte levels, liver function tests (LFTs)
3. Computed tomography (CT) of the chest, abdomen, and pelvis with intravenous (IV) contrast
4. Positron emission tomography (PET)-CT if limited disease is suspected
5. Magnetic resonance imaging (MRI) or CT of the brain with IV contrast
6. None of the above; all are necessary

Image courtesy of Wikimedia Commons.

Answer: F. None of the above; all are necessary.

All of the steps listed in answers A, B, C, D, and E are required for full lung cancer staging. In addition, mediastinoscopy may be required, as well as bone marrow biopsy and bone scanning to differentiate limited-stage from extensive-stage disease. This broader distinction between limited-stage and extensive-stage disease (shown) is commonly employed to guide treatment of SCLC.^[2]

Lung cancer comprises several histologic subtypes, which are associated with differing management approaches and prognoses.^[3] The pie chart in this slide depicts these histologic subtypes and their relative frequency; in addition, it further divides each group of patients into nonsmokers and smokers, as defined by a current history, a former history of smoking, or a 1-year history of smoking.

Image courtesy of Wikimedia Commons. Data from Kenfield SA et al.^[3]

The table in this slide outlines typical immunostaining patterns for various histologic subtypes of lung cancer.^[4]

Table adapted from Wikimedia Commons, antibody Sam Shlomo Spaeth.

SCLC often appears peripherally as well as centrally. The axial CT scan in this slide shows peripheral SCLC in the right lung.

Image courtesy of Medscape.

This slide shows a cross-section of a lung specimen obtained from a smoker with SCLC. The white area is the tumor, and the black area is lung tissue that has been affected by smoking.

Image courtesy of Wikimedia Commons.

The scanning electron micrograph in this slide shows a lung cancer cell dividing.

Which of the following statements regarding SCLC is not true?

1. SCLC is generally very aggressive, exhibits rapid growth, and can quickly become metastatic
2. SCLC is associated with distinct paraneoplastic processes, such as Lambert-Eaton syndrome, ectopic adrenocorticotropic hormone (ACTH) production, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and hypercalcemia
3. SCLC is associated with mutations, such as exon 19 deletion, exon 21 substitution, and epidermal growth factor receptor (EGFR) mutation
4. SCLC often spreads to the adrenals and the brain
5. Most SCLCs are due to prior cigarette smoking
6. SCLC is the second most common cause of malignancies in the United States for both males and females

Image courtesy of Wikimedia Commons.

Answer C. SCLC is associated with mutations, such as exon 19 deletion, exon 21 substitution, and epidermal growth factor receptor (EGFR) mutation.

Such mutations are more commonly associated with NSCLC. The brain is a common site of spread for SCLC. This slide shows a contrast-enhanced axial MRI scan of the brain of a patient known to have SCLC; two ring-enhancing lesions are visible in the periventricular region.

Image courtesy of Medscape.

The frontal chest radiograph in this slide shows a left-midlung deposit that extends into the left upper lobe. A right-middle-lobe nodule is visible as well. Extensive peritracheal lymphadenopathy is also noted.

Image courtesy of Medscape.

The bones are a common site for spread in SCLC. This slide shows a whole-body bone scan from a patient with SCLC, with anterior and posterior views. Radiotracer uptake is visible in the spine, the ribs, the left scapula, and the pelvis, indicating metastatic bony disease.

Which of the following statements is not true?

1. Between 30% and 40% of patients with SCLC have disseminated or extensive-stage disease on presentation
2. Extensive-stage SCLC is generally incurable
3. In limited-stage SCLC, combination chemotherapy plus chest radiation can result in a median survival of approximately 17 months
4. Indicators of poor prognosis include weight loss exceeding 10% of body weight, poor performance status score, and relapsed disease

Image courtesy of Medscape.

Answer: A. Between 30% and 40% of patients with SCLC have disseminated or extensive-stage disease on presentation.

As noted on slide 6, approximately two thirds of patients with SCLC have extensive-stage disease on presentation.

This slide shows a CT scan at the level of the hilum from a patient with SCLC. A large hilar tumor can be seen on the right side, as well as pleural thickening, indicative of pleural metastasis. A loculated pleural effusion is also visible adjacent to the tumor mass in association with an atelectatic lung.

Image courtesy of Medscape.

Progression of SCLC can cause increased pressure on the mediastinal structures, which can lead to further complications.^[5]

Which of the following may develop as a result of this increased pressure on the mediastinal structures?

1. Superior vena cava (SVC) syndrome
2. Hoarseness from compression of the recurrent laryngeal nerve
3. Hemidiaphragmatic paralysis from compression of the phrenic nerve
4. Dysphagia from compression of the esophagus
5. Stridor from compression of the major airways
6. All of the above

Image courtesy of Wikimedia Commons.

Answer: F. All of the above.

The adrenal glands are also a common site of spread for SCLC. This slide shows a nonenhanced CT scan of the abdomen at the level of the adrenals. A large left adrenal mass with associated hypoattenuation can be seen. In a patient with SCLC, this finding is likely to represent metastatic disease.

Image courtesy of Medscape.

This slide shows a contrast-enhanced axial CT scan from a patient with known SCLC. Innumerable hypoattenuating liver lesions are present. In view of the history of SCLC, the hypoattenuating liver lesions, and the indistinct borders of the liver lesions, it is very likely that this patient has metastatic SCLC.

With respect to limited-stage SCLC, which of the following statements is not true?

1. Limited-stage SCLC should fit within two radiation "ports"
2. Limited-stage SCLC is generally stage I-III (T1-2, any N, M0) disease that can be treated with definitive chemotherapy and thoracic irradiation
3. The goal of treatment for limited-stage SCLC is to achieve cure of the disease
4. PET-CT can be used to rule out distant metastasis
5. Pleural involvement indicates extensive-stage disease

Image courtesy of Medscape.

Answer: A. Limited-stage SCLC should fit within two radiation "ports."

As noted on slide 6, limited-stage disease should fit within one radiation field.^[2]

This slide shows a coronal PET scan from a patient with SCLC. Increased uptake is visible in the left hilum and the left adrenal; this probably represents metastatic SCLC.

Image courtesy of Medscape.