A 56-year-old white man was seen in December 2007 for evaluation of a
lung mass. The patient presented with chronic cough that prompted a chest
X-ray. The X-ray showed a nodule in the right upper lobe. His past medical
history was significant for hyperlipidemia and gastroesophageal reflux disease.
His medications were atorvastatin (Lipitor, Pfizer),ranitidine
hydrochloride (Zantac, GlaxoSmithKline) and aspirin. The patient did not have
any family history of cancer. He had a 40 pack-year smoking history and uses
He had no past exposure to asbestos or chemicals. He denied shortness of
breath, weight loss, headaches, dizziness or bone pain. Physical exam did not
reveal any cervical, supraclavicular or axillary adenopathy. Cardiac and
respiratory examination was normal.
His initial complete blood count and complete metabolic panel were
normal. Chest CT revealed a 1.6 cm nodule involving the right upper lobe with
cavitation. His PET/CT scan showed increased radiotracer uptake in the right
upper lobe. In addition, he was found to have a lesion in his left adrenal
gland that was suspicious for metastatic disease. MRI of the brain was normal.
Because since the adrenal gland appeared to be the only site of
metastatic disease, resection of the primary tumor and a metastasectomy were
planned for an attempt to cure. The patient underwent a video-assisted
thoracoscopic mediastinoscopy in January 2008, and the frozen section of the
mass showed moderately differentiated adenocarcinoma.
Because since the frozen section did not reveal any positive lymph
nodes, the patient then underwent resection of the right upper lobe. One month
later, he underwent laparoscopic left adrenalectomy. The final pathology of the
adrenal gland was consistent with metastatic adenocarcinoma. His final
pathologic staging was T1N0M1. The patient then completed four cycles of
adjuvant chemotherapy with cisplatin and vinorelbine in May 2008.
A follow-up CT scan in October 2008 showed interval increased
enhancement and modest size increase in a subcentimeter right adrenal nodule
compared with Feburary 2008. A CT scan in January 2009 showed appearance of
numerous small subcentimeter pulmonary nodules bilaterally and continued
enlargement of a contrast-enhancing right adrenal mass measuring 1.7 cm,
compatible with adrenal metastasis.
PET scan showed increased uptake only in the right adrenal gland. The
patient was enrolled in a clinical trial and was treated with sorafenib
(Nexavar, Bayer) and pemetrexed (Alimta, Eli Lilly). Treatment was discontinued
after two cycles due to mixed response, with improvement in pulmonary nodules
but disease progression by RECIST criteria (26% increase) in the size of
The patient was then treated off-protocol with pemetrexed and
bevacizumab (Avastin, Genentech) in March and has completed 10 cycles thus far.
His last CT scan from November shows stable disease with no appreciable change
in the size of the adrenal mass compared with March.
Although adrenal glands are a common metastatic site for nonsmall
cell lung cancer, metastatic involvement limited to the adrenal gland alone is
rare and represents 1.6% to 3.5% of patients presenting with resectable NSCLC.
Metastases typically represent widespread systemic dissemination of disease and
are associated with poor prognosis. Palliative chemotherapy is generally the
accepted method of treatment. Over the last several years, numerous reports and
studies have demonstrated that long-term survival after resection of isolated
metastasis, such as brain metastasis, can be achieved in selected patient
populations when the primary thoracic involvement is early-stage and
potentially curable, ie, T1/2N0. A similar approach, but to a lesser extent,
has been used in patients presenting with isolated adrenal metastasis as well.
One of the hypotheses for isolated adrenal metastases is that such cases
may arise from direct lymphatic spread of the primary lung tumor via
retroperitoneal channels representing a locoregional spread, in contrast to
systemic spread. An isolated adrenal metastasis is usually defined as a
synchronous metastasis if it is diagnosed within six months of the diagnosis of
the primary lung cancer. It is deemed a metachronous metastasis if it occurred
more than six months from the time of diagnosis of NSCLC.
In a multicenter study of 43 patients, reported by Porte et al, median
survival of patients who underwent adrenalectomy was 11 months. Three patients
survived longer than five years, suggesting that surgical treatment of solitary
adrenal metastasis from resectable NSCLC could potentially improve survival. In
this report, there was no significant difference in survival between
synchronous and metachronous presentation of adrenal metastases.
In some series, the disease-free interval, which refers to the time from
diagnosis of the primary lung cancer until the diagnosis of adrenal metastases,
is prognostic. In a study published in the Journal of Clinical
Oncology, Tanvetyanon did a retrospective analysis of studies on
survival outcomes of adrenalectomy for NSCLC patients. Median overall survival
was shorter for patients with synchronous metastasis than those with
metachronous metastasis (12 months vs. 31 months, P=.02). The cause for
decreased survival among synchronous tumors is probably secondary to the
intrinsic biology of the tumors, in that those presenting as synchronous
lesions grow faster or are more aggressive.
Surgical complications from adrenalectomy were infrequent in the case
series. Studies have indicated that laparoscopic procedures yielded similar
results to open procedures, but with less morbidity and a shorter hospital
stay. However, the procedure may be limited by the size of the metastasis.
For a lesion 4.5 cm or smaller, survival is equivalent between open
adrenalectomy and a laparoscopic approach. Few reports have been published on
the role of radiotherapy on adrenal metastases. Soffen and colleagues reported
the results of palliative radiotherapy in nine patients with lung carcinoma and
an isolated adrenal metastasis, whose median survival was six months.
A key concern in patients presenting with synchronous metastasis is to
establish that the adrenal metastasis is truly isolated when the lung cancer
itself is otherwise resectable. Management of isolated adrenal metastasis in
the context of advanced disease stage intrathoracically (eg, N2 or N3 nodal
involvement), which in itself has a poor prognosis, should be approached on a
case-to-case basis with the disease-free interval as an important criterion in
In patients with clinical stage I or II NSCLC and a supposedly solitary
adrenal metastasis, preoperative staging should at least include a PET scan,
brain MRI and mediastinoscopy to exclude more advanced stages of disease.
In conclusion, adrenalectomy can be considered for some patients
presenting with isolated adrenal metastasis and may improve survival in a
selected group of patients, particularly in those with long disease-free
Ramya Varadarajan, MD, is a Medical Oncology Fellow at Roswell Park
Cancer Institute, Buffalo, N.Y., and is a member of the HemOnc
Today Editorial Board. She would like to acknowledge Dr. Grace Dy for
her guidance and support.
Why lung metastases should have a predilection for tiny adrenal glands
is enigmatic. We previously suggested that the slow-flow portal venous
structure of the gland (two capillary transitions) may entrap vaso-occlusive
tumor emboli. A similar hypothesis can be proferred for the
Waterhouse-Friderichsen syndrome of venous occlusive hemorrhage into the gland
in complement-activating septic patients, patients in whom C5a aggregates
vaso-occlusive granulocyte masses.
Harry S. Jacob, MD
HemOnc Today Chief Medical Editor
For more information:
- Ettinghausen SE. J Clin Oncol. 1991;9:1462-1466.
- Porte HL. Ann Thorac Surg. 2001;71:981-985.
- Porte HL. Ann Thorac Surg. 1998;65:331-335.
- Shahidi H. Chest. 1996;109:271-1276.
- Soffen EM. Cancer. 1990;65:1318-1320.
- Tanvetyanon T. J Clin Oncol. 2008;26:1142-1147.