Keywords
inflammatory myofibroblastic tumor - histopathology - anaplastic lymphoma kinase -
pediatric surgery
Introduction
An inflammatory myofibroblastic tumor (IMT) is a soft tissue neoplasm that predominates
in children and young adults.[1]
[2]
[3] In total, 50% of all documented benign primary pulmonary neoplasms in a pediatric
population are IMTs.[1] Nevertheless, pulmonary IMT still remains a unique presentation, given the rarity
of primary pulmonary tumors in this population in general.
IMT was first described in 1939 as a benign lung tumor with contradictory histopathology.[1] Given its fibro-inflammatory aspect and the believe it originated from a post-inflammatory
repair process, it was later classified under the umbrella term “inflammatory pseudotumor
(IPT).”[3] Afterwards, the origin of IMT remained debatable for decades. At the end of the
1990s, the detection of chromosomal abnormalities made it clear that IMT must be seen
as a true neoplasm.[4]
[5]
[6] First, it was classified as a benign neoplasm, but nowadays the World Health Organization
(WHO) describes IMT as a lesion of intermediate malignant potential.[7]
We present a case of a young boy with pulmonary IMT.
Case Report
A 6-year-old boy with hyperreactive airways and a history of prolonged post-viral
coughing presented with recurrent respiratory infections for over a month. Since the
age of 2, he received a fluticasone/propionate inhaler as maintenance therapy.
In the weeks prior to diagnosis, he suffered from two respiratory tract infections
with high fever and myalgia. Each was followed by a prolonged period of severe coughing,
with the child remaining pale and weakened afterwards. A few cervical lymph nodes
were noticed. Lung auscultation was normal. The laboratory tests were compatible with
a viral infection: leukopenia with lymphocytosis and normal C-reactive protein. A
chest radiograph showed an image of bronchitis and a lesion of 18 mm in the right
upper lobe ([Fig. 1]). The lesion was absent on a chest radiograph 3 years earlier.
Fig. 1 Chest X-ray and computed tomography (CT) scan showing a lesion in the right upper
lobe.
A computed tomography (CT) scan was performed, which showed a well-defined solitary
nodule of 16 mm in the right upper lobe ([Fig. 1]). Radiological differential diagnosis suggested a hamartoma, carcinoid tumor or
metastasis. An abdominal ultrasound, serum tumor markers, and a catecholamine dosage
on 24-hour urine were normal with the exception of a slightly elevated neuron-specific
enolase (21 µg/L).
A whole-body CT scan and a positron emission tomography scan were conducted, with
the lesion showing a selective hypermetabolism, and therefore suggesting a malignant
entity. Meanwhile, the clinical image resolved, and the patient could resume his normal
activities.
One month after first presentation, a video-assisted thoracoscopic (VATS) right upper
lobectomy with lymph node resection was performed. The patient weighted 23.7 kg at
the time of surgery. The procedure was achieved by an uniportal incision above the
sixth rib. The surgeon used 3 and 5 mm material. Segmental arteries were either stapled
or coagulated. Upper lobe vein and bronchus were stapled. The total operative time
was 2 hours and 33 minutes. There were no postoperative complications and 4 days after
surgery, the patient was discharged.
On histopathological examination, the lesion was 17 mm in size, tan and firm with
a smooth surface. Tumor-free section margins were at least 5 mm. All resected lymph
nodes were found to be negative. Microscopic examination of the nodule showed spindle
cells in a background of plasma cells ([Fig. 2]). Foamy histiocytes, lymphocytes, and eosinophils were sporadically seen. No nuclear
atypia or elevated mitotic activity was observed. Anaplastic lymphoma kinase (ALK)
immunohistochemical expression was negative. KI67 staining was not performed. Based
on these data, the diagnosis of plasma cell granuloma IMT was made.
Fig. 2 Histopathological examination of the lesion in different magnifications: (A) nonencapsulated, well-circumscribed tumor nodule surrounded by normal lung parenchyma
(HE staining, Bar = 1 mm). (B) On higher magnification, the tumor is made of fibrous fascicules mixed with chronic
inflammatory cells and a few vessels (HE staining, bar = 50 micron). (C) On highest magnification, the tumor is made of fibrous fascicles mixed with numerous
plasma cells and a few eosinophils. No atypia, no significant mitotic activity (HE
staining, bar = 20 microns). Inclusion of a few normal alveolar structures are not
shown.
The follow-up period lasted one and a half years, during which no local or distant
recurrence was observed.
Discussion and Conclusion
We describe an incidental finding of IMT in the right upper lobe in a 6-year-old boy.
Although IMT occurs at any age, it predominately occurs in children and adolescents.[1]
[2]
[3]
[8] Lesions are typically 10 to 60 mm in size, round, well-demarcated, and slowly growing.[2] They are mostly found in the lungs but can develop in any organ, including the mediastinum,
urinary bladder, ovary, liver, kidney, gastrointestinal tract, and soft tissues.[2]
[8]
[9] When in the lung, parenchymal IMT generally outweighs the prevalence of endobronchial
lesions.[2]
[4]
Symptoms depend strongly on the tumor's location.[2] Pulmonary IMT usually presents with fever and cough, often accompanied by respiratory
distress, arthralgia, clubbing, night sweats, vomiting, and hemoptysis.[10] Central IMTs tend to be recognized earlier.[11] Frequently IMT is a coincidental finding, as many patients remain asymptomatic.[8]
While spontaneous regression has been reported, the therapy of choice remains surgical
excision.[3]
[9]
[12] In this case, a VATS lobectomy was combined with systematic lymph node dissection
as mediastinal metastases have been described.[13] A complete resection is considered curative with no adjuvant treatment necessary,
as local recurrence after radical excision is a rare event.[2]
[9]
[10]
[14] Chemotherapy is generally ineffective but could be indicated when IMT is complicated
with local invasion or recurrence.[6]
[8]
[14] ALK inhibitors can provide durable responses in unresectable or metastatic ALK-expressing
IMT, although relapses due to secondary ALK mutations have been reported.[14]
[15]
[16] Treatments with immunotherapy, nonsteroidal anti-inflammatory drugs, and steroids
are reported with various results.[10]
[16]
[17]
Histologically, IMT consists of three different presentations (xanthogranuloma, plasma
cell granuloma, and sclerosing pseudotumor type), but these patterns are of no clinical
importance and can even coexist in the same lesion.[18] Because of this fibro-inflammatory aspect, IMT was long considered an IPT. Presently,
it is believed that IMT is a true neoplasm.[4]
[5]
[6] The etiology remains unclear. Griffin et al discovered in 1999 recurrent abnormalities
on chromosome 2 at 2p23 with alterations near or within the ALK gene.[4]
[5] Many kinds of chimeric ALK genes have been reported so far.[19] These translocations result in an overexpression of tyrosine kinase receptor ALK.
Anti-ALK antibodies, a specific marker for abnormal ALK gene expression by immunohistochemistry,
are detected in 50% of all IMTs.[11]
[14]
Expression of ALK is higher in younger patients and in extrapulmonary IMT.[8]
[14] The presented case lacked ALK expression, aligning with Camela et al's study, which
found that only 16% of reviewed pulmonary IMTs were ALK-positive.[10]
ALK-positive tumors have a less than 5% risk of metastasis, as opposed to ALK-negative
lesions, which are more prone to distant spread.[6]
[14] Despite ALK-positive lesions being more locally aggressive and have a tendency to
local recurrence, ALK expression is considered a favorable prognostic indicator due
to the rarity of local recurrence after radical excision.[9]
[10]
[17]
These chromosomal alterations, in combination with a more locally aggressive behavior
of ALK-positive IMT, have led to the belief that IMT is a true neoplasm.[5]
[14] Currently the WHO describes IMT as a lesion of intermediate malignant potential,
because of the risk of local recurrence and distant metastasizing.[7] Long-term follow-up remains indicated, as cases of relapse are described several
years after primary surgery.[2] There are no established guidelines for pulmonary pediatric IMT follow-up; therefore,
we propose a protocol based on standard oncology protocols, using magnetic resonance
imaging (MRI) to minimize radiation exposure: a chest X-ray at 3 and 6 months postresection,
followed by yearly MRI starting 1 year after surgery.
Pulmonary IMT is a rare disease and could be missed given the nonspecific symptoms
at presentation, especially in peripheral lesions. It should always be considered
in the differential diagnosis of a primary pulmonary lesion in children and young
adults. To confirm the diagnosis, histopathological examination is mandatory. Primary
surgery is the treatment of choice with a good overall survival rate in case of complete
resection. Nevertheless, prolonged follow-up of these patients remains necessary due
to the intermediate malignant potential.
