Surgical Science, 2011, 2, 427-429
doi:10.4236/ss.2011.28093 Published Online October 2011 (
Copyright © 2011 SciRes. SS
Leptomeningeal Carcinomatosis Presenting Early in
Non-Small Cell Lung Cancer
Ezra N. Teitelbaum1, Susan M. Hasselquist2, Imad A. Tabbara3, Gregory D. Trachiotis1*
1Division of Cardiothoracic Surgery, the George Washington University
Medical Center Department of Surgery, Washington DC, USA
2Division of Hematology and Oncology, the George Washington University
Medical Center Department of Surgery, Washington DC, USA
3Division of Pulmonary, Critical Care and Allergy, the George Washington University
Medical Center Department of Surgery, Washington DC, USA
E-mail: *
Received June 16, 2011; revise d August 20, 2011; accepted Septembe r 22, 201 1
Purpose: we present the case of a patient presenting with altered mental status on post-operative day seven
after a diagnostic lung biopsy. The diagnosis of carcinomatous letomeningeal metastasis was confirmed.
Methods: we discuss meningeal carcinomatosis in lung cancer, and describe challenges to diagnosis, therapy,
and prognosis. Results: a review of the literature describing the clinical and oncologic principles of leto-
meningeal carcinomatosis in lung cancer is performed. Discussion: leptomeningeal carcinomatosis (LC) oc-
curs in approximately 5% of patients with non-small cell lung cancer and incurs a bleak prognosis. Pre-
senting neurologic symptoms can be varied and diagnosis is confirmed via lumbar puncture and cerebrospi-
nal fluid cytology. Few data exist regarding optimal treatment, although intrathecal chemotherapy has been
shown to provide a modest improvement in median survival.
Keywords: Leptomeningeal Carcinomatosis, Lung Cancer
1. Introduction
Leptomeningeal metastasis is an increasing complication
of non-small cell lung cancer (NSCLC), occurring with
an estimated incidence of approximately 5% [1]. Wide-
spread dissemination of tumor cells throughout the men-
inges and ventricles can also be seen in 5% of cases with
adenocarcinoma of the breast, gastrointestinal tract, me-
lanoma, childhood leukemia and systemic lymphoma
[1-3]. Most often leptomenineal carcinomatosis (LC)
presents in patients with cancer at the time when sys-
temic disease has recurred or when prior chemotherapy
regi mens have faile d. T hus, t h e goa l of tr eat ment fo r LC,
if initiated, is often to control or preserve neurologic
performance, while attempting to attenuate other wide-
spread systemic disease and palliation. For NSCLC, the
presentation of a neurologic process without brain par-
enchymal involvement early in the diagnosis is espe-
cially rare and unusual. This report details such a case,
and describes current best modalities for diagnosis and
palliative therapy.
2. Case Report
A 50 year old woman had a left upper lobe opacity found
incidentally on a chest x-ray performed during a hospi-
talization for an anaphylactic reaction to a bee sting. The
patient had no history of cough or shortness of breath,
and no recent weight loss or bone pain, and did not
smoke or have a family history of lung cancer. On
physical examination the vital signs were normal, lungs
were clear, neurologic exam was normal and there was
no skeletal tenderness or palpable lymphadenopathy. A
computed tomography (CT) scan of the chest revealed an
isolated 2.2 cm spiculated lesion in the left upper lobe
and no mediastinal adenoapthy (Figure 1). Positron
emission tomography (PET) scan demonstrated hyper-
metabolic activity in the lung mass, as well as multiple
hypermetabolic skeletal lesions in the left humerus, L1
and L3 vertebral bodies and right and left iliac bones all
consistent with metastatic disease. A CT scan of the
brain was normal without evidence of metastases.
Modalities of obtaining a tissue diagnosis, including
Figure 1. Chest CT showi ng the left upper lo be mass.
percutaneous biopsy of the lung or bony lesions or a sur-
gical lung biopsy, were discussed and the patient opted
to proceed with surgery. The patient had a left video-
assisted thoracoscopic segmental resection of the left
upper lobe mass, and pathology confirmed the mass to be
a 2.2 cm moderately differentiated adenocarcinoma.
Clinical, pathologic and radiographic studies classified
the patient as Stage IV non-small cell lung cancer. Post-
operatively the patient complained of an unusual amount
of nausea and intense headaches. Her neurologic exam
remained normal, a magnetic resonance imaging (MRI)
of the brain obtained at this time was normal. Her symp-
toms improved with anti-emetics and a change in pain
regimen and she was discharged home after chest tube
removal on post-operative day three.
On post-operative day seven the patient was brought
back to the emergency room after complaining of severe
frontal headaches and then becoming increasingly
somulent. On exam the patient had a temperature of 36.5,
heart rate (HR) of 45, blood pressure (BP) of 155/80. She
was drowsy and arousable to voice but not oriented and
not able to follow commands. Her motor, sensory and
cranial nerve exams were without focal deficits. A head
CT revealed diffusely enlarged ventricles and an MRI
showed increased meningeal enhancement in the poste-
rior parietal and occipital lobes suggestive of meningitis
(Figure 2). A lumbar puncture was performed with an
opening pressure of 41 cm. The drained cerebrospinal
fluid (CSF) was clear with 9 leukocytes (90% lympho-
cytes) and 2 erythrocytes per µL. The patient was admit-
ted to the intensive care unit and started on intravenous
vancomycin, ceftriaxone and acyclovir. Her mental
status temporarily improved but overnight she became
obtunded with a HR of 38 and a BP of 175/80. A repeat
head CT was unchanged and a lumbar drain was placed.
With interval drainages of CSF, the patient’s mental
Figure 2. MRI wi th meninigeal en hancement in t he pariet al
and occipital lobes.
status, HR and BP returned to normal. CSF cultures re-
mained negative and cytology returned showing metas-
tatic adenocarcinoma cells. Antibiotics were discontin-
ued and the patient was started on intrathecal meth-
otrexate through the lumbar drain. A ventricular reser-
voir and mediport were placed for further administration
of intrathecal (thiopeta) and systemic chemotherapy
(premetrexed and carboplatin), and she was discharged
home. After the fourth cycle of systemic therapy, a re-
peat PET scan showed no change in the metastatic
skeleta l lesions. Fo ur months after diagno sis she has lo st
10 pounds and continues to have headaches but remains
without other neurologic or respiratory symptoms.
3. Discussion
Of the 10% - 15% of patients with neurologic metastatic
lung cancer, approximately 5% of patients with non-
small cell lung cancer will develop leptomenigeal carci-
nomatosis (LC) (or metastatic infiltration of the CSF).
This is usually a later finding in patients who have al-
ready failed systemic chemotherapy regimens, although
it can also be present at the time of initial diagnosis [1,2].
Patients with leptomenigeal carcinomatosis (LC) can
present with symptoms similar to infectious meningitis
such as headache, somulence, neck stiffness, nausea and
vomiting. Alternatively, direct nerve invasion can pro-
duce cranial nerve palsies or blood vessel infiltration can
result in stroke-like patterns of extremity weakness [3].
CT scan of the head with intravenous contrast is used
to rule out brain metastases and signs of increased in-
tracranial pressure. MRI with gadolinium contrast can
better evaluate for metastatic disease and detect signs of
Copyright © 2011 SciRes. SS
Copyright © 2011 SciRes. SS
LC such as meningeal enhancement [3,4]. While imaging
can serve as a useful guide, CSF histology remains the
gold standard for diagnosis of LC. CSF cytology is posi-
tive for malignant cells in 50% - 70% of cases, although
this yield can be increased to 90% with second and third
lumbar punctures. Increased opening pressures, high
protein and low glucose levels are also common findings
on CSF examination [5].
LC remains a bleak diagnosis with median survivals of
one to five months in treated patients and four to six
weeks if left untreated [2,6,7]. Wasserstrom reviewed 90
patients with LC from various primary tumors treated
with intrathecal methotrexate. The 23 patients with all
type lung cancer primaries had a 50% response rate and a
median survival of 4 months [6]. Chamberlain studied a
selective population of patients with LC from non-small
cell lung cancer primaries. These 32 patients were treated
with intrathecal methotrexate and some received in-
trathecal cytarabine and thiotepa as second and third-line
therapies respectively. Twelve of the patients received
concurrent systemic chemotherapy. Complete cytologica l
and partial clinical responses were seen in 43% of pa-
tients treated with methotrexate, 50% of those treated
with cytarabine and 33% of those treated with thiotepa.
Median survival was five months and no difference was
seen in the patients who also received systemic chemo-
therapy [2]. Other therapies used in LC have included
gemcitabine and ara-C, as well as radiotherapy and sur-
gery to palliate compressive brain or spinal cord metas-
tases [8].
4. Conclusions
LC is a rare complication of non-small cell lung cancer
that imparts a dismal prognosis. Diagnosis is made by
imaging and CSF evaluation with cytology. Treatment
with intrathecal chemotherapy results in a small im-
provement in life expectancy. As such, palliation of
symptoms and discussions with patients and their family
members regarding realistic expectations for prognosis
are important aspects of care.
5. References
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