Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report.

Abstract

Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously.
We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later.
Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma.

Full text

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CASE REPORTOpen Access
Non-small cell lung carcinoma in an adolescent
manifested by acute paraplegia due to spinal
metastases: a case report
Ulrike Ackert1, Dieter Haffner1,2and Carl Friedrich Classen1*
Abstract
Introduction: Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have
been reported previously.
Case presentation: We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma
(squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor
overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the
bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult
protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation
and second-line docetaxel. After a transient response our patient experienced disease progression and died about
10 months later.
Conclusion: Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small
cell lung carcinoma.
Introduction
Lung cancer is the leading cause of cancer-related mor-
tality in adults in many countries, especially in smokers
[1,2]. There are small cell and non-small cell lung can-
cers (NSCLC). NSCLC are subdivided into adenocarci-
nomas (about 50%), squamous cell (about 20%), large
cell (about 10%), and otherwise not defined carcinomas
[1]. The TNM staging system is closely associated with
prognosis. Metastatic disease, defined as stage IV,
accounting for 10% to 20% of cases, has a median survi-
val time of nine months and a five-year survival of
about 1% [2]. The peak age for NSCLC is 50 years to 60
years [2]. Recently, several molecular characteristics of
NSCLC, including p53 mutations, epidermal growth fac-
tor receptor (EGFR) mutations with subsequent dysre-
gulation of the ras/raf kinase pathway and k-ras
mutations, have been defined [3], leading to some tar-
geted therapy approaches. Their benefit is still not quite
clear [4,5].
The therapy options–surgery, chemotherapy, irradia-
tion and targeted therapy–are usually applied according
to the TMN staging and the molecular signature [3-5].
Tumors should be resected primarily whenever possible
[6]. Unresectable tumors imply a palliative condition.
Combination first-line chemotherapy is used to obtain
maximum efficacy, eventually combined with radiother-
apy. In second-line treatment, monotherapy is proposed
for patients in an appropriately good condition [4,6].
For first-line therapy, cisplatinum-based chemotherapy
plus radiotherapy is superior to radiotherapy or che-
motherapy alone [6,7]. Several agents have been applied
in addition to cisplatinum, for example paclitaxel, doce-
taxel, gemcitabine, pemetrexed, vinorelbine and irinote-
can. Gemcitabine is regarded as first choice in
squamous cell carcinomas by most authors [7]. For sec-
ond-line therapy, monotherapy, for example with doce-
taxel, is common. Usually, an aggressive therapy would
now be inappropriate [7].
In the last years, targeted therapies have shown antitu-
moral effects. Most targets are related to EGFR or the
raf/ras kinase signaling, since deregulation of this path-
way is common in NSCLC [3,7]. Both EGFR-targeted
* Correspondence: cfclassen@gmx.de
1University Children’s Hospital Rostock, Ernst-Heydemann-Strasse 8, D-18057
Rostock, Germany
Full list of author information is available at the end of the article
Ackert et al. Journal of Medical Case Reports 2011, 5:486
http://www.jmedicalcasereports.com/content/5/1/486
JOURNAL OF MEDICAL
CASE REPORTS
© 2011 Ackert et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
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antibodies, for example cetuximab, and kinase inhibitors,
like erlotinib, have a low toxicity, however, their efficacy
depends on the signaling pathway deregulation [3,7].
Antibodies against the vascular-endothelial growth fac-
tor receptor (VEGFR) are efficient in non-squamous cell
tumors [1].
Lung carcinomas in patients below 20 years of age are
extremely rare. Here, we report the case of a 16-year-
old boy with a non-small cell, squamous cell bronchial
carcinoma T4N2M1 initially presenting with paraplegia
due to spinal metastases. In spite of all therapeutic mea-
sures performed according to adult treatment protocols
our patient experienced only a transient response, fol-
lowed by disease progression, and died about nine and
half months after diagnosis.
Case presentation
Our patient was the second child of non-consangui-
neous healthy parents, both Caucasian (ethnically Ger-
man); his sister was healthy. Three cases of carcinomas,
including a bronchial carcinoma, had been observed in
grandparents and an aunt.
He was born after an uneventful pregnancy and
showed normal development except for mild attention
deficit disorder. He never smoked nor abused other sub-
stances, nor was he exposed to tobacco smoke, chemi-
cals or irradiating toxins.
At the age of 16 years, eight weeks before initial pre-
sentation, he experienced an episode of back pain fol-
lowed four weeks later by unproductive cough with
minimal hematoptysis. A chest X-ray showed a discrete
central infiltrate. Two weeks before admission he had
several episodes of back pain. Finally, the boy had
experienced a numb feeling in the lower body half from
about thoracic vertebra (Th) seven downwards, loss of
strength and insecure gait for two days prior to admis-
sion. Pain sensitivity and tendon reflexes were preserved.
Strength was grade four in his legs and feet. A shar-
pened breath murmur of amphoric type was heard.
Otherwise, the boy was in a stable condition with a nor-
mal examination status.
Magnetic resonance imaging (MRI) of his spine, fol-
lowed by computed tomography (CT) of his chest (Figures
1 and 2) showed an acute transverse myelocompression at
Th5 by a tumor with intraspinal extensions, and a central
intrapulmonary lesion infiltrating both main bronchi. An
emergency laminectomy with subtotal tumor resection
was performed with stabilization by a fixateur interne. A
histological analysis showed a non-small cell squamous
bronchial carcinoma (NSCLC), EGFR amplification and k-
ras mutation negative. Staging included a bronchoscopy
with biopsy of an intrabronchial tumor portion, a bone
scan, MRI and CT. An inoperable lung tumor, with metas-
tases at Th5 and in his os sacrum and left scapula, was
diagnosed, in other words, stage IV, T4N2M1. A familiar
p53 mutation and a germ cell tumor were excluded. Com-
plete laboratory and clinical workup showed no infections,
immunodeficiency or drug addiction.
Treatment was initiated according to current recom-
mendations for adults. Six cycles of intravenous
Figure 1 MRI of the thoracic spine, in sagittal view, T1-
weighed image with contrast medium enhancement. The tumor
leads to significant myelocompression, and grows infiltratingly into
the surrounding tissue.
Figure 2 CT scan of his lungs, showing a large central space
occupying lesion surrounding both main bronchi.
Ackert et al. Journal of Medical Case Reports 2011, 5:486
http://www.jmedicalcasereports.com/content/5/1/486
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cisplatinum (70 mg/m2/d, day one) and gemcitabine
(1000 mg/m2/d, day one and day eight) were given
three-weekly, with a bisphosphonate (pamidronate, 30
mg) every four weeks. New generation EGFR or signal-
ing inhibitors were not applied since k-ras mutation and
EGFR overexpression and/or mutation were negative.
After four weeks, local progression of the sacral metas-
tasis led to ischial nerve irritation requiring extended
analgetic medication (opioids plus pregabalin). Fractio-
nated sacral irradiation with 30 Gy soon induced analge-
sia. Clinical tumor progress at Th5 developed at about
three months, confirmed by MRI, which led to neurosur-
gical resection of a regrown metastasis. Since it was not
feasible to separate irradiation of the main bronchial
tumor and the area of Th5, combined fractionated irra-
diation with 30 Gy was subsequently performed.
Toxicity of the six cycles of cisplatinum and gemcita-
bine over the first four months following diagnosis con-
sisted of vomiting (WHO III°), infection (WHO II°),
tricytopenia (WHO III°) and cachexia (WHO III°),
requiring home parenteral nutrition.
Now, a chest CT scan showed shrinkage of the main
bronchial tumor but also appearance of pleural lesions,
likely to represent metastases. Thus it appeared inap-
propriate to proceed with gemcitabine and cisplatinum,
since our patient wanted a less toxic therapy.
In accordance with recommendations for second-line
therapy in adults, the boy received docetaxel (75 mg/
m2/d every three weeks) as monotherapy for four and a
half months after diagnosis. However, disease progres-
sion developed one month later with new spinal metas-
tases at Th12, L1, L2 and L4. Another course of
palliative irradiation was given for analgesia. Besides
cachexia, the boy suffered from febrile chills and cough
and a pleural effusion. About seven months after diag-
nosis, chemotherapy was discontinued to preserve qual-
ity of life as much as possible.
About eight months after diagnosis, the boy presented
with double vision, headache and diabetes insipidus. A
CT scan of his head revealed numerous brain metas-
tases. Palliative dexamethasone was initiated.
Further multimodal palliative care was provided and
our patient lived until about nine and a half months
after diagnosis and died at home.
Discussion
Since 1876, when McAldowie first described a case of
lung cancer in a five-month-old child [8], the disease
has only occasionally been reported in children and ado-
lescents. Published series include different histological
entities including carcinoids, mucoepidermoid carcino-
mas, inflammatory pseudotumors, and others; only a
minority are squamous cell carcinomas [9-11]. In 1977
and 2003, two series of 24 and 92 patients, respectively,
with lung cancer below 40 years were published, with
only one patient below 20 years in each. Their prognosis
was similar to that of older patients [12,13]. Analyzing
26 patients below 30 years, Mizushima et al. [14] found
a more favorable prognosis in the young patients, how-
ever, there was a low incidence of squamous cell carci-
noma and a predominance of stage I.
The largest series of pediatric lung cancer was col-
lected in a 1983 meta-analysis [15]. In 151 malignant
lung tumors, beside many carcinoids and lymphomas,
47 were bronchogenic carcinomas, including six squa-
mous cell tumors.
In conclusion, the published literature on pediatric
squamous NSCLC is too sparse to draw any clear con-
clusion as compared with the older population.
In our case, several questions remain unanswered.
First, why did the boy develop the disease in the first
place? Neither the analysis of the tumor itself, nor the
anamnestic or clinical workup gave any indication as to
cause; in particular, no toxin exposure, immunodefi-
ciency or familial disposition could be identified.
The second question is whether the exceptionally young
age of our patient was associated with any special disease
features. We found that histology, genetics, distribution,
type of response and time course of the disease were simi-
lar to what is observed in older patients. Finally, it has to
be asked whether any other treatment options might have
been effective in our patient. More than six cycles of cis-
platinum and gemcitabine chemotherapy in combination
with irradiation, as first-line standard therapy for NSCLC
patients, are rarely tolerated. Equally, the irradiation given
as palliative focal treatment of painful bone metastases fol-
lowed by tumor field irradiation after tumor shrinkage by
initial chemotherapy represent a common approach in
adults. So it may only be speculated whether further addi-
tion of a targeted drug might have been beneficial. Rando-
mized studies indicate that drugs targeting the EGFR or
ras/raf kinase pathway are only effective in cases with
deregulation of these pathways [3]. Other treatment mod-
alities or strategies that might have helped the boy do not,
to our best knowledge, exist.
Conclusion
Taken together, in the case reported here, we observed a
stage IV NSCLC in a 16-year-old boy, in which the
course of the disease was as may be expected in typical
cases contracting the disease at an older age.
Consent
Written informed consent was obtained from the
mother (legal guardian) of our patient for publication of
this case report and any accompanying images. A copy
of the written consent is available for review by the Edi-
tor-in-Chief of this journal.
Ackert et al. Journal of Medical Case Reports 2011, 5:486
http://www.jmedicalcasereports.com/content/5/1/486
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Acknowledgements
The authors gratefully acknowledge the permission by Prof. Hauenstein,
Radiolology Clinic, University of Rostock, to use the images.
Author details
1University Children’s Hospital Rostock, Ernst-Heydemann-Strasse 8, D-18057
Rostock, Germany.2Department of Pediatric Kidney, Liver, and Metabolic
Diseases, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625
Hannover, Germany.
Authors’ contributions
UA analyzed and interpreted the patient data regarding the clinical
presentation. DH added particular background information and was a major
contributor in writing the manuscript. CFC performed basic organization of
the writing and clinical data collection. All authors read and approved the
final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 23 May 2011 Accepted: 28 September 2011
Published: 28 September 2011
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doi:10.1186/1752-1947-5-486
Cite this article as: Ackert et al.: Non-small cell lung carcinoma in an
adolescent manifested by acute paraplegia due to spinal metastases: a
case report. Journal of Medical Case Reports 2011 5:486.
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