A 45-year-old male with about a 30 pack-year history of smoking
presented to his primary care physician in March 2010 with a cough of few days
He had no other significant past medical problems. He was a construction
worker and his review of systems was unremarkable.
He was treated conservatively and his symptoms did not improve. Chest
X-ray showed vague opacities in the right upper lobe. He was scheduled for a CT
scan, but in the interim, he developed neck and facial swelling that got worse
within a few days. He developed respiratory distress and was admitted to the
hospital. Physical exam revealed multiple palpable bilateral supraclavicular
and cervical lymph nodes with decreased air entry to the right lung and
He also was noted to have dilated veins on the chest and some facial
puffiness. He was diagnosed with superior vena cava (SVC) syndrome and was
admitted to the ICU. A CT scan of the chest and PET CT showed extensive
mediastinal adenopathy with compression of superior vena cava and compression
of proximal airways with trachea narrowing (Figure 1).
Figure 1A. Axial and coronal images of the CT demonstrating
extensive mediastinal mass with compression of the SVC. The mass also was
compressing the trachea and proximal airways.
He underwent a left cervical lymph node biopsy, which revealed small
cell carcinoma (Figure 2). He also had some enlarged lymph nodes in the upper
abdomen around the gastrohepatic space and para celiac regions. Fine needle
aspiration cytology of the abdominal node was inconclusive but suspicious for
malignancy. Complete blood count and comprehensive metabolic panel were
Further metastatic workup with nuclear bone scan and MRI of the brain
did not show any evidence of metastasis. He had a normal chromogranin A level
but increased neuron-specific enolase at 16.4 mcg/mL (normal range: 3.7-8.9
mcg/mL). He was staged as having extensive-stage small cell lung cancer (SCLC).
He was treated with six cycles of cisplatin and etoposide and whole-brain
He had an excellent response to chemotherapy with improvement in his
symptoms. Post-treatment CT scan showed significant decrease in size of
mediastinal and abdominal lymph nodes. His post-treatment blood work showed
decreased neuron-specific enolase, and he was placed on active surveillance. He
died of recurrent disease about 1 year after presentation.
SCLC is associated with heavy tobacco use and accounts for about 13% of
newly diagnosed lung cancers each year. About 28,500 cases of SCLC are
diagnosed each year.
SCLC is a cancer of neuroendocrine origin, occurring in the central
airways and characterized by rapid growth with significant mediastinal
adenopathy. Common clinical symptoms include cough, chest discomfort, dyspnea,
hemoptysis, weight loss, fatigue, malaise and anorexia. Severe cases can
present as SVC syndrome.
SCLC is associated with paraneoplastic syndromes in about 50% of cases.
The most common neuroendocrine features include ectopic adrenocorticotropic
hormone secretion, causing Cushings syndrome in severe cases, and
syndrome of inappropriate antidiuretic hormone hypersecretion, causing
hyponatremia that could be life-threatening in extreme cases.
Other paraneoplastic syndromes with SCLC include Lambert-Eaton
myasthenic syndrome, a syndrome of sensory neuronopathy/multifocal
encephalomyelitis and cerebellar degeneration, limbic encephalitis and
cancer-associated retinopathy. Pathological diagnosis is made by light
microscopy, which shows round to fusiform small-sized cells with scant
cytoplasm with finely granular nuclear chromatin and absent or inconspicuous
nucleoli with extensive necrosis.
Immunohistochemistry can be helpful in difficult cases. Tumor markers
such as lactate dehydrogenase, chromogranin A and neuron-specific enolase may
be elevated. Radiological features include bulky mediastinal mass on chest CT
with post-obstructive pneumonitis or collapse, bronchial encasement,
compression or obstruction and, sometimes, associated pleural effusion and/or
Figure 1B. A) Axial fusion image at the level of the
mediastinum from PET/CT demonstrating enlarged and hypermetabolic mediastinal
and bilateral hilar lymph nodes up to 1.9 cm in the short axis, with maximum
standard uptake value (SUV) of 3.4. B) Fusion image from the same scan at the
level of the upper lobes demonstrating hypermetabolic right upper lobe opacity
with maximum SUV of 3.5.
The most commonly used classification is the Veterans Administration
Lung Study Group (VALG) staging system, in which the disease is subdivided into
limited stage (LS) and extensive stage (ES).
LS-SCLC is disease confined to one hemi-thorax with involvement of the
ipsilateral and/or contralateral mediastinal and/or in the ipsilateral
supraclavicular lymph nodes that can be encompassed within a reasonable
radiation field. ES-SCLC is defined as disease that extends beyond the
hemithorax. Ipsilateral malignant effusions are defined as having LS-SCLC
according to the original VALG definition, but they are considered to have
ES-SCLC by many cooperative groups.
LS-SCLC accounts for about 40% of the patients with SCLC and is a
potentially curable disease. The treatment of choice is concurrent
chemoradiotherapy, with a 5-year survival rate of about 25%. Workup for
metastasis includes PET CT, nuclear medicine bone scan and MRI of the brain.
Tumor markers chromogranin A and neuron-specific enolase are helpful in
monitoring the disease activity and response to treatment. The standard
chemotherapeutic agents used are a combination of cisplatin and etoposide.
However, carboplatin is used as an alternative agent to cisplatin in patients
who cannot tolerate or have a contraindication.
ES-SCLC has very poor prognosis, with average survival of about 10
months, despite excellent response to chemotherapy. Common chemotherapeutic
regimens include a platinum-based regimen with combination of cisplatin and
etoposide or topotecan.
The incidence of central nervous system metastases in SCLC patients is
about 50%. Prophylactic cranial irradiation is recommended in ES-SCLC and in
patients who obtain a near complete or complete response to chemotherapy for
patients with LS-SCLC, as it reduces the incidence of brain metastases and
Radiation therapy also has a role in the symptomatic management of the
brain metastasis and to relieve airway obstruction in cases of severe central
airway compression. There is some data to suggest the use of continuing the
chemotherapy after initial chemotherapy in patients with ES-SCLC with
improvement of PFS but without improved OS.
Surveillance after the initial treatment includes history and physical
exam every 3 to 4 months, along with chest imaging, during the first 2 years,
every 6 months during the next 3 to 5 years, and then annually.
Docetaxel, irinotecan, gemcitabine, paclitaxel, ifosfamide and topotecan
are some of the second-line chemotherapeutic agents used for the relapsed
disease. The prognosis is more guarded in this setting, with about 20% to 30%
response, and with median survival of weeks to months.
Figure 2. A) The tumor has totally replaced the lymph node and
shows extracapsular extension. B and C) This high-grade neoplasm is composed
predominantly of sheets of large, hyperchromatic cells, with high N/C ratio,
salt and pepper type chromatin and inconspicuous nucleoli. The tumor shows a
high mitotic rate and areas of necrosis and extensive apoptosis. Nuclear
molding and crash effect (D) is also identified.
Images courtesy of M. Ghesani, MD
SVC syndrome is caused by the invasion or extrinsic compression of the
vena cava by adjacent pathologic processes, especially by the mass in the
middle or anterior mediastinum, usually consisting of enlarged right
paratracheal lymph nodes, lymphoma, thymoma, an inflammatory process or an
aortic aneurysm, or by internal thrombus of SVC.
Lung cancer is the leading malignant cause of SVC syndrome, with
nonsmall cell lung cancer accounting for about 50% of the cases and SCLC
accounting for about 25% of cases occurring in malignancy.
The superior vena cava carries blood from the head, arms and upper body
to the heart. Compression of the superior vena cava resulting in obstruction
will cause blood flow through the collaterals to the lower body through the
azygous vein or inferior vena cava.
Obstruction of the SVC causes increased venous pressure in the upper
body, resulting in edema of the head, neck and arms, which is visually striking
but without significant morbidity. Severe cases can present with laryngeal
edema, causing dyspnea, stridor, cough, hoarseness and/or dysphagia. It also
can cause cerebral edema, leading to cerebral ischemia, confusion, coma and,
It is considered a medical emergency, and the management of the SVC
syndrome associated with malignant disease includes both treatment of the
cancer and relief of the symptoms of obstruction. Major therapeutic modalities
are supportive care and medical management, including chemotherapy,
radiotherapy, placement of intravascular stent and surgery.
Very little progress has been made in the past 30 years with
chemotherapy agents. Newer chemotherapeutic agents that showed some promise in
early-phase clinical trials include amrubicin (a third-generation
anthracycline), vinorelbine, vinflunine and pemetrexed.
Also, some targeted therapies have shown some activity with chemotherapy
backbone. These include antiangiogenic agents such as bevacizumab (Avastin,
Genentech), vandetanib (IPR Pharms), sorafenib (Nexavar, Bayer) and aflibercept
(Eylea, Regeneron), growth factor receptor pathway inhibitors such as imatinib
(Gleevec, Novartis) and temsirolimus (Torisel, Wyeth), and proteasome inhibitor
bortezomib (Velcade, Millennium Pharmaceuticals).
It will be interesting to see how these newer agents affect the
management of SCLC.
Munir Ghesani, MD, is an attending radiologist at St.
Lukes-Roosevelt Hospital Center and Beth Israel Medical Center, an
associate clinical professor of radiology at Columbia University College of
Physicians and Surgeons, and a HemOnc Today section editor.
Rangaswamy Chintapatla, MD, is a fellow in hematology and oncology at
St. Lukes Roosevelt Hospital Center. Anupama Goel, MD, is an
attending physician in the division of hematology and oncology at St.
Lukes Roosevelt Hospital Center. Sam Altman, MD, is a resident in
radiology at St. Lukes-Roosevelt Hospital Center. Zheng Ma, MD, is
a resident at St. Lukes-Roosevelt Hospital Center.
For more information:
- Allen J. Clin Lung Cancer. 2008;9:262-270.
- Dowell JE. Am J Med Sci. 2010;339:68-76.
- Drivsholm L. Br J Cancer. 1999;81:667-671.
- National Comprehensive Cancer Network Practice Guidelines in
Oncology. Small cell lung cancer. Available at: www.nccn.org/professionals/physician_gls/PDF/sclc.pdf.
Accessed Jan. 14, 2012.
- Stinchcombe TE. Oncologist. 2010;15:187-195.
- Wilson L. N Engl J Med. 2007;356:1862-1869.