Keywords
inflammatory - fibroid - polyp - intussusception
Introduction
Inflammatory fibroid polyp (IFP) represents one of the rarest causes of polypoid disease
of the gastrointestinal (GI) tract in childhood. It is characterized by submucosal
fibrous connective tissue growth with spindle-shaped cells in a hypervascular stroma
infiltrated by nonspecific inflammatory cells, especially eosinophils. After its first
report by Vanek in 1949,[1] the lesion has been described by various names, including “Vanek's tumour,” eosinophilic
or submucosal granuloma, gastric fibroma with eosinophilic infiltration, inflammatory
pseudotumor, and hemangiopericytoma, with the term IFP (proposed in 1953) currently
widely accepted.[2] The lesions are usually solitary and may be located anywhere across the GI tract.
The etiopathogenesis, as well as the origin of the mesenchymal spindle-shaped cells
that comprise the polyp remains enigmatic. Recent studies though have shown familial
occurrence of the polyps,[3] expression of platelet-derived growth factor receptor (PDGFRA), and oncogenic PDGFRA mutations in the majority of these tumors,[2]
[4]
[5] suggestive of a neoplastic nature. We present a rare case of a child with an IFP
of the terminal ileum, who presented with intussusception.
Case Report
A 10-year-old boy was referred for a surgical opinion, with worsening symptoms of
intermittent abdominal pain associated with drowsiness that started 10 days prior,
after a 24-hour period of diarrhea. Medical history included some features of Noonan
syndrome including short stature for which treatment with growth hormone had been
commenced. On presentation, he was hemodynamically stable and well hydrated. Abdominal
examination revealed the presence of a tender cylindrical mass in the epigastrium,
with no signs of peritonism. Inflammatory markers were normal. Abdominal ultrasound
showed the presence of a complex, multilayered mass in the epigastrium, with features
suggestive of intussusception. Because of the complex nature of the lesion, a computerized
tomography scan of the abdomen was also performed and that showed a complex multilayered
cystic and solid mass, approximately 8 × 5 cm lying inferior to, compressing and displacing
a thick-walled inflamed stomach. Imaging findings could not exclude the presence of
an internal hernia, or gastric or small bowel volvulus. Emergency laparotomy was performed,
at which an ileocolic intussusception in the epigastrium was found with an intraluminal
mass in the terminal ileum as a focal point. The intraoperative impression was that
the lesion represented a lymphoma therefore a right hemicolectomy with ileocolic anastomosis
was performed. The patient recovered well from surgery.
Histopathology reported the presence of a large polypoid mass with a fleshy red surface
in the terminal ileum (3.5 × 3 × 2.5 cm). The polyp showed surface ulceration with
granulation tissue on the surface ([Fig. 1]), but with the polyp itself arising from the submucosa and being composed of spindle
cells in a loose fibromyxoid stroma. The stroma had rich inflammatory mainly eosinophilic
infiltrate and thin collagen bundles with variably ectatic blood vessels ([Fig. 2]). There was no atypia or mitotic features. Immunohistochemistry excluded inflammatory
myofibroblastic tumor (negative for Alk1, desmin, SMA), GIST (negative for CD117),
and schwannoma (negative for S100). The lesion was positive for CD34 and faintly for
vimentin. Overall, the appearances were typical of an IFP, completely excised. Cytogenetic
studies with fluorescence in situ hybridization were done to exclude rearrangement
of the Alk gene (anaplastic lymphoma kinase) which is identified in inflammatory myofibroblastic
tumors and some colorectal carcinomas. Mutations in the PDGFRA gene were not assessed in this analysis.
Fig. 1 A polyp, cut open, showing surface ulceration.
Fig. 2 Lesion is composed of spindle-to-stellate-shaped cells in an oedematous stroma. There
is prominent inflammatory infiltrate composed of lymphocytes and eosinophils (Inset
right lower corner).
The patient has been symptom-free after a year of follow-up, and remains under clinical
surveillance.
Discussion
Although these lesions were regarded in the past to be reactive overgrowths of fibrovascular
tissue, recent data have shown that they are rather PDGFRA-driven benign neoplasms, as 55 to 65% of them have been proven to carry mutations
in the PDGFRA gene.[4]
[5] They are extremely uncommon in childhood as they tend to affect patients after the
5th to 6th decade of life.[6]
[7] A total of 14 cases have been identified in the literature[6]
[8]
[9]
[10]
[11]
[12] ([Table 1]). The lesion can affect the whole of the GI tract, with the stomach most commonly
involved in adults, but in children the distribution seems to be slightly different
with most cases reported to occur in the ileum (five cases), with intussusception
as the main presentation (four cases). Other symptoms related to the lesions are generally
nonspecific, and the polyps may manifest themselves with anemia caused by occult GI
bleeding, abdominal pain or vomiting, and less frequently with rectal bleeding, intestinal
obstruction, or failure to thrive.[6]
[7]
[8] The polyps are virtually impossible to diagnose preoperatively as their imaging
features are nonspecific. Even if endoscopy is undertaken, biopsy may be difficult
as the lesions are usually sessile arising from the submucosa with surface erosion
and granulation. Therefore, diagnosis is usually established after complete excision
of the polyp, which is usually considered intraoperatively to be a lymphoma due to
the resulting inflammation. Complete excision is almost always therapeutic and the
reported recurrences mainly occurred in patients in whom resection was attempted endoscopically.[7]
[12]
Table 1
Case reports of pediatric IFPs
|
No.
|
Author
|
Year
|
Age (y)
|
Sex
|
GI location
|
Clinical features
|
|
1
|
Samter[8]
|
1966
|
4
|
M
|
Colon
|
Pain, vomiting, perforation
|
|
2
|
Samter[8]
|
1966
|
8
|
F
|
Jejunum
|
Vomiting, diarrhea, anemia
|
|
3
|
McGreevy et al[9]
|
1967
|
2
|
F
|
Ileum
|
Intussusception
|
|
4
|
Persoff[8]
|
1972
|
3
|
M
|
Ileum
|
Pain, vomiting, diarrhea
|
|
5
|
Pollice[8]
|
1984
|
8
|
M
|
Rectum
|
Lower GI bleeding, anemia
|
|
6–9
|
Blackshaw and Levison[6]
|
1986
|
N/A
|
N/A
|
N/A
|
No details mentioned for pediatric cases
|
|
10
|
Schroeder[8]
|
1987
|
5
|
F
|
Stomach
|
Pain, vomiting, anemia
|
|
11
|
Montgomery and Popek[10]
|
1994
|
N/A
|
N/A
|
Ileum
|
Intussusception
|
|
12
|
Dabral et al[11]
|
2003
|
7
|
M
|
Ileum
|
Intestinal obstruction
|
|
13
|
Chongsrisawat et al[8]
|
2004
|
4
|
F
|
Stomach
|
Anemia, fever
|
|
14
|
Saïji et al[12]
|
2006
|
15
|
M
|
Ileum
|
Intussusception
|
Abbreviations: F, female; GI, gastrointestinal; IFP; Inflammatory fibroid polyp; M,
male.
Despite various proposed theories, the origin of the polyp's spindle cells remains
largely unknown. As eosinophilic infiltration was one of the most constant findings,
an allergy-based pathogenesis was proposed, and hence, the name eosinophilic granuloma.
In most cases, although there is no history of allergy and eosinophilia is present
in only 4% of the patients, while eosinophilic infiltration can be associated with
other GI diagnoses, such as eosinophilic gastroenteritis.[6] Other proposed etiologies included neural hyperplasia,[13] leiomyomatous origin,[14] and metabolic disorders similar to Hand-Schuller-Christian disease or Letterer-Siwe
syndrome,[15] although the most common theory was that the polyps formed as an inflammatory granulomatous
reaction to a variety of potential gut insults including trauma, infection or reactions
to chemicals, initiating the proliferation of fibroblasts, inflammatory, and stromal
cells.[16] The report of familial occurrence with multiple and recurrent IFPs in a family,[3] as well as the recognition of PDGRFA gene mutations in exons 12 or 18[2]
[4]
[5] has changed the perception regarding these polyps, which are now considered to represent
true neoplasms. The PDGFRA gene encodes a receptor tyrosine kinase, and activating mutations in exons 12, 14,
and 18 have been found in GISTs and possibly represent a potent oncogenetic event.[2]
[4] PDGFRA-related GISTs are usually epithelioid and less aggressive but can still recur and
produce metastases.[4]
[5] IFPs are benign neoplasms with no risk or recurrence or metastasis after complete
removal, but the identification of a common genetic defect implies a common oncogenetic
pathway with GISTs. It is very interesting that Schildhaus et al actually report a
case of simultaneously occurring IFP and GIST.[5] Despite these advances, the nature of the tumor cells remains a mystery and the
origin of the submucosal mesenchymal progenitor cell that mutates to develop the tumor
is still unknown.
Differential diagnosis is difficult even at a microscopic level, and comprehensive
immunohistochemical analysis is employed to differentiate from other tumors such as
GIST, mesenchymal sarcoma, schwannoma, and inflammatory myofibroblastic tumor. The
latter is a rare mesenchymal neoplasm of the gut, positive to desmin, SMA, and Alk1
stains that is associated with locally invasive disease, lack of mitoses-atypia, recurrence
rates between 18 and 40%, and a risk of malignant transformation.[17] In our case, CD34 stain which is a commonly used marker of hematopoietic progenitor
cells and endothelium was positive, as is in GISTs, but CD117 was negative. Vimentin
stain, which is a marker of mesenchymal origin, was also positive.
It is not yet clear whether the classification of IFPs as a mesenchymal benign neoplasm
has implications for treatment or follow-up, because in the vast majority of the reported
cases, surgical excision alone was curative, and no reports exist of a malignant transformation.
Because of the unknown yet origin of the lesion, the rarity of the disease in childhood
and the relative absence of literature data for the disease, a cautious approach with
periodic clinical surveillance of the affected children seems reasonable, with follow-up
endoscopy reserved only for cases of endoscopically removed polyps.
