Research Article
Primary Lung Tumors in Children and Adolescents: 29 Years of Experience at a Single Institution
Fazal N Wahid1, Alpin D Malkan1, Armita Bahrami2, Alberto S Pappo3, John A Sandoval1, Israel
Fernandez-Pineda1 and Bhaskar N Rao1*
1Department of Pediatric Surgery, King Saud Medical City, Riyadh Saudi Arabia
2Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA
3Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA
*Corresponding author: Bhaskar N Rao, Department of Surgery, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
Published: 11 Oct, 2017
Cite this article as: Wahid FN, Malkan AD, Bahrami A,
Pappo AS, Sandoval JA, Fernandez-
Pineda I. Primary Lung Tumors in
Children and Adolescents: 29 Years of
Experience at a Single Institution. Clin
Surg. 2017; 2: 1666.
Abstract
Purpose: Primary lung tumors in children are rare and comprise a broad range of histopathologic
types. The incidence and outcome of these lesions are still largely unknown. We investigated the
relative incidence of different primary lung tumors and their outcomes in children and adolescents
at a single pediatric institution.
Methods: All patients diagnosed with primary lung tumors from 1984 through 2013 were
retrospectively reviewed. Data were collected from medical records after approval was obtained
from our Institutional Review Board.
Results: Seventeen-patients (8 boys, 9 girls) were identified with a mean age of 9.3 years (range:
newborn to 18 years). Seven distinct histopathologic tumor types were identified: inflammatory
myofibroblastic tumor (4), pleuropulmonary blastoma (4), carcinoid (n=3), mucoepidermoid
carcinoma (2), synovial sarcoma (1), pulmonary hamartoma (2), and infantile fibrosarcoma (1).
Chemotherapy was used in 37.5% (n=6) and radiation in 25% (4) of patients. The mortality rate
was 25% (n=4), but only two deaths (12.5%) were directly related to the lung tumors. Of the 12
survivors, median duration of follow-up was 8.75 years (range, 0.5-20.4 years). One patient was lost
to follow-up.
Conclusions: Our experience substantiates the rarity and histopathological diversity of primary
lung tumors in pediatric patients. Although complete resection remains the standard of care for
most lung tumors, the role of adjuvant therapy is dependent on the histopathologic tumor type.
Introduction
Primary pulmonary neoplasms are rare in children and are far more likely to be metastatic disease or inflammatory/congenital in nature. The ratio of primary to metastatic to inflammatory/ congenital tumors is reported to be 1:5:60 [1]. The various pediatric pulmonary tumors differ in their prevalence and outcome. Another complicating factor is the evolution of the histopathologic classification system. The current World Health Organization (WHO) system differs substantially from many historical classification systems, as new tumors have been described (Pleuropulmonary Blastoma [PPB]), other tumors have been reclassified from benign to malignant (Inflammatory Myofibroblastic Tumor [IMT]), and still other tumors are more rare than once believed (rhabdomyosarcoma) [2-4]. In 1982, Hartman and Shochat reviewed 230 cases of primary pediatric pulmonary tumors described in the English-language literature [5]. Since that publication there have been several large, single-institution series reported [1,6-11]. The purpose of this article is to review and describe our experience over a 50-year period.
Methods
A single-institution retrospective chart review was performed with the approval of the St. Jude Children’s Research Hospital Institutional Review Board (IRB). Medical records of all patients diagnosed with a primary, non-hematologic pulmonary neoplasm were reviewed from 1962 through 2013.
Results
Demographics
Between 1962 and1983 there were no patients identified with a primary lung tumor. From 1984-2013 seventeen-patients were identified (8 boys, 9 girls) with a mean age at diagnosis of 9.3 years (range: newborn to 18 years). Table
1 summarizes the demographic and clinical data. A total of seven
distinct histopathologic pulmonary tumor types were identified.
Tables 2 and 3 describe treatment and outcome data, respectively.
Inflammatory myofibroblastic tumor
Four patients (23.5%) had IMF. The first patient had been
treated for Hodgkin lymphoma 2 years before the diagnosis of IMF.
Pulmonary wedge resection was performed without any additional
therapy, and remained disease-free at 20.4 years. The second patient
had a history of being treated for peripheral neuroectodermal tumor
also underwent pulmonary wedge resection. Unfortunately the
patient was also found to have myelodysplastic syndrome/AML
which proved fatal. The third patient had bi-lobectomy and is disease
free at 10.2 years. The fourth patient underwent lobectomy but
developed recurrence and subsequently received chemotherapy. The
patient remains disease free at 2.8 years.
Pleuropulmonary blastoma
Four patients (23.5%) had PPB. The first patient underwent
lobectomy, and was disease-free at 6.1 years of follow-up. The second
patient underwent pneumonectomy in addition to chemotherapy
and radiation, and remained disease-free at 19.9 years. Longterm
complications included scoliosis from the thoracotomy
and restrictive pulmonary disease due to radiation therapy. The
third patient underwent pulmonary wedge resection at a different
institution with gross spillage of tumor during surgery. The patient
developed recurrence after one year which was treated with surgery,
chemotherapy, and radiation. Despite these efforts the patient
died within 2 years from initial diagnosis. The fourth patient had a
lobectomy followed by chemotherapy and radiation, and was disease
free at 17.7 years. Unfortunately the patient developed scoliosis,
sternal and chest wall hypoplasia due to radiation.
Carcinoid tumor
Three patients (17.6%) had carcinoid tumors. Two patients
underwent lobectomy and one patient had bronchoscopic laser
ablations.The patient who underwent multiple bronchoscopic laser
ablations, remained disease free after five years since last ablation.
The bronchial surgical margins of one patient was positive after bilobectomy,
however, the decision was made to perform scheduled
clinical follow-up and imaging in addition to bronchoscopy as
the positive margins were at birfurcation of bronchus. The patient
remains disease-free after 0.5 year. One patient was lost to follow-up.
Mucoepidermoid carcinoma
Two patients (11.7%) had mucoepidermoid carcinoma. One
patient underwent lung biopsy and died within one month of
diagnosis. The second patient had lobectomy and did not require
adjuvant therapy. The patient remains disease-free at 7.3 years of
follow-up.
Pulmonary hamartoma
Two patients (11.7%) had a pulmonary hamartoma, and both
underwent pulmonary wedge resections. The first patient had
metastatic osteosarcoma, and during thoracotomy for metastatectomy,
one nodule was identified as hamartoma. This patient died due to
the initial disease. The second patient had a primary diagnosis of
craniopharyngioma with subsequently development of osteosarcoma
and myelodysplastic syndrome. An evaluation for bone marrow
transplantation revealed a pulmonary nodule that was resected
(wedge) and a hamartoma was found. This patient was disease-free at 3 years.
Synovial sarcoma
One patient (5.8%) had a pleural-based synovial sarcoma.
The patient underwent pneumonectomy and received adjuvant
chemotherapy and radiation. The patient remains disease-free at 13.5
years.
Infantile fibrosarcoma
One patient (5.8%) had a lung mass at birth and underwent
lobectomy. He was diagnosed as infantile fibrosarcoma. The patient
developed recurrence after 2 years and underwent pneumonectomy
and chemotherapy. The patient developed scoliosis secondary to
pneumonectomy, however, remains disease-free at 19.2 years. The
overall mortality rate was 25% (n=4) in our series, however, only
2 deaths (12.5%) were attributable to the primary lung tumors.
Chemotherapy was used in 37.5% cases (n=6) and radiation in 25%
(n=4). Of the 12 survivors, the median duration of follow-up was
8.75 years (mean: 10.5 years; range: 0.5-20.4 years) at the time of this
review. One patient was lost to follow-up.
Discussion
The histopathologic diagnosis of primary pediatric lung tumors
has evolved significantly during the past several decades. In their
1982 review of the literature, Hartman and Shochat [5] described
230 tumors comprising 16 histopathologic subtypes. In contrast, the
current WHO histologic classification of lung tumors now consists
of 41 distinct epithelial entities (31 malignant and 10 benign) [3],
illustrating how the distinction of these tumors has advanced. For
years, the proportions of malignant and benign primary lung lesions
have been accepted as 66% and 34%, respectively. However, the most
common “benign” tumor, IMT, has been reclassified as malignant
[3]. With this change, the cohorts reviewed by Hartman and Shochat
[5] and 10 years later by Hancock and colleagues [9] would have had
a malignant tumor frequency of 85% to 90%, consistent with the 86%
observed in our series.
Carcinoid tumors have been reported to account for 11% to 20%
of all pediatric pulmonary tumors [5,9,11] which is consistent with
18.5% in our series. The outcome of carcinoid tumor is dependent on
the extent of disease at presentation [12]. Five-year survival estimates
for local, regional, and disseminated disease are 81%, 77%, and 26%,
respectively [13]. Our one patient who was lost to follow-up had
localized tumor, suggesting a good prognosis; the second patient also
had localized disease and remained disease-free at last follow-up.
Salivary gland tumors consist of mucoepidermoid, adenoid cystic,
epithelial-myoepithelial carcinomas, and in adults, these tumors
represent less than 0.2% of primary lung tumors and are associated
with a poor prognosis (39% survival at 5 years) [14]. In children, as
many as 10% of primary pulmonary tumors are of the salivary gland
histologic types, and the prognosis is favorable [8,11,15]. In our series
there were 2 patients with mucoepidermoid carcinomas where one
died within 1 month after diagnosis, and the second who underwent
lobectomy remained disease-free at last follow-up. IMF, previously
known as plasma cell granuloma and inflammatory pseudotumor,
has traditionally been considered a benign entity. However, the
WHO has recently recognized IMT as a low-grade mesenchymal
malignancy. A significant proportion of IMTs have demonstrated
ALK1 gene mutations, and the tumors are currently regarded as
malignant neoplasms [16]. Treatment of pulmonary IMT is based on
surgical resection, although these can rarely recur, have invasion of
adjacent organs, and lead to death [17,18]. The two patients in our
series underwent pulmonary wedge resection. One was disease-free at
last follow-up ( 20.4 y), while the second died of acute myelogenous
leukemia. The two patients who underwent lobectomy were both
disease free at last follow-up. However, one patient had recurrence
and ultimately received chemotherapy. Of the 7 cases reported by
Yu et al. [11], 2 had wedge resection, 2 required lobectomy, and 3
had pneumonectomy. Two of the tumors recurred, and one patient
died during anesthesia induction for resection of recurrent tumor.
Chemotherapy, radiation, and anti-inflammatory medications have
been proposed as adjuvant therapies, however, no single regimen is
generally accepted. The term PPB was first used in 1988 by Manivel
and colleagues. These blastemic pediatric pulmonary tumors had
previously been grouped with adult pulmonary blastomas. Three
subtypes of PPB have been described on the basis of gross features.
Type I is cystic and lacks a solid component; conversely, type III is
solid and lacks a cystic component, while type II is a mixture of solid
and cystic. Outcomes were generally poor, with a 2-year survival
estimate of 63% overall (type I, 80%; type II, 73%; type III, 48%).
However, outcomes improved with time and in recent report from
International Pleuropulmonary Blastoma Registry 5 year OS for type
I is 91%, type II 71% and type III is 53% [19]. A germline mutation in
DICER1 is the genetic cause in the majority of PPB cases. However,
DICER 1 mutation was not related to outcome [19].Treatment
previously advocated by Parsons et al. [20] depends on aggressive
surgery followed by chemoradiotherapy. Although the reported
effectiveness of local radiotherapy varies, some studies suggest that
it is helpful when resection is incomplete [21,22]. Our three cases of
PPB had a disease-free follow-up of 6.1, 17.7 and 19.9 years, and two
patients received radiation and chemotherapy. The fourth patient underwent lobectomy, chemotherapy and radiation for recurrence,
and died after 2 years from initial diagnosis. Pulmonary sarcomas
are extremely rare, constituting only 0.1% of all primary lung
malignancies. Their histogenesis is not well understood, but they are
thought to arise from immature mesenchymal cells. The prognosis of
pulmonary synovial sarcoma is poor, with a 5-year survival estimate
of 50%. Our series included two patients, both of them were disease
free till last follow up.
Table 1
Table 2
Table 3
Conclusion
Our experience substantiates the rarity and histopathological diversity of primary lung tumors in pediatric patients. Although complete resection remains the standard of care for most tumors, the role of adjuvant therapy is dependent on the histopathologic tumor type.
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