Pulmonary involvement in NF-1 occurs in up to 20% of the cases, and
fibrosis and thin-walled bullae formation, predominantly in upper zones are the
most common pulmonary manifestations [
2,
3].
It has been suggested that the genetic abnormality responsible for NF-1
increases a patient's risk of various kinds of malignancies, and therefore,
individuals with NF-1 have a significantly higher incidence of malignant
schwannoma, neurofibrosarcoma, intracranial glioma, and pheochromacytoma
[8]. However, association of primary lung carcinoma with NF-1 is not common
[7]. A Japanese review reported only 11 cases of NF-1 with primary lung
carcinoma until 1992 [6]. Adenocarcinoma was the most frequent histologic
diagnosis (72.9%) in this report as well as in most of the recent surveys of lung
cancer in Japanese population [9]. We found a few more cases in the medical
literature presenting this association, and interestingly, those were also from
Japanese researchers [5,6,10-13]. The questions raising from these reports
are; whether that occurrence of primary lung adenocarcinoma in these patients
with NF-1 is coincidental, or there is an increased risk for the development of
lung adenocarcinoma in patients with NF-1. Since NF-1 is not a very rare
disease and adenocarcinoma is the most frequent histologic type among
reported primary lung carcinomas, coincidental association of lung
adenocarcinoma with NF-1 might be possible. On the other hand, the
hypothesis of the increased risk for primary lung adenocarcinoma in NF-1 can
be explained by two different mechanisms: 1) most of these reports addressed the possibility that adenocarcinoma might be originating from previous scar
tissue or bullae wall because the tumor was usually in the upper lobes where
bullae and scar tissues were predominant in NF-1 [13-15]; 2) NF-1 is the most
common inherited syndrome predisposing to neoplasia, and individuals with
NF-1 have a significantly higher incidence of neural crest derived-tumors,
particularly benign neurofibromas, malignant schwannoma, neurofibrosarcoma,
intracranial glioma, and pheochromocytoma, so there might be also an
increased risk for the development of primary lung carcinoma in NF-1 [8]. Latter
has been investigated in some genetic based studies which were not able to
show a strong relation but some evidences to support this hypothesis. NF-1
gene has been mapped to a small region of chromosome 17q [4]. Therefore,
many surveys were conducted to show any genetic linkage between the
abnormalities on chromosome 17 and the malignant transformation in NF-1
[5,6,16]. In a study by Menon et al [16] deletions of chromosome 17 in NF-1-
derived tumor specimens were searched. While no loss of markers on
chromosome 17 was observed in any of the benign tumors from NF-1 patients,
17p but not 17q deletions were observed in neurofibrosarcomas. This region is
known to contain a candidate gene, P53, which has been implicated in the
progression of a broad spectrum of human cancers including lung carcinomas
[5]. Most recently, a highly significant association between P53 mutations and
deletions on 17p was found in the pathogenesis of non-small cell lung
carcinomas [17]. In accordance with these findings, a loss of heterozygosity on
chromosome arm 17p, but not 17q, in small cell lung carcinoma from a patient
with NF-1 was detected in a subsequent study by Shimuzi et al [5]. And it was
suggested that inactivation of tumor suppressor gene on chromosome 17p,
most likely P53, might be responsible for the development of small cell lung
carcinoma in their patient with NF-1.
On the basis of these findings, one can speculate that the risk for the
development of primary lung carcinoma in NF-1 might be increased at least in
some patients due to increased prevalence of deletions on chromosome arm
17p.
In our case, the tumor was originated from the left lower lobe bronchi and
there was no association with scar tissue or bullae formation excluding the
possibility of a scar carcinoma. Since, our patient was a non-smoker young man
and there was no family history of a previous cancer, whether this was a
coincidental association, or development of the lung adenocarcinoma was
associated with the increased genetic susceptibility of NF-1 is not certain.
We specifically presented this case because of the rare association of NF-1
and primary adenocarcinoma of the lung. We suggest that the lung
adenocarcinoma in our case was not originated from a scar tissue, and the
linkage between these two entities should be further investigated in genetic
based studies.
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