Characteristic of inflammatory myofibrinoblastic tumor: Retrospective analysis of 4 cases in children hospital number 2

Bệnh viện Trung ương Huế 
70 Journal of Clinical Medicine - No. 64/2020
Case Report
CHARACTERISTIC OF INFLAMMATORY MYOFIBRINOBLASTIC 
TUMOR: RETROSPECTIVE ANALYSIS OF 4 CASES IN CHILDREN 
HOSPITAL NUMBER 2
Dao Thi Thanh An1,2*; To Thuy Nhi2; Nguyen Dinh Van2; 
Nguyen Thi Thanh Truc3; Truong Dinh Khai4
DOI: 10.38103/jcmhch.2020.64.10
ABSTRACT
Introduction: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that involves 
various organs. Surgery is the mainstay of therapy for this tumor. Approximately half of all IMT cases have 
anaplastic lymphoma kinase (ALK) rearrangements; therefore, the ALK inhibitor crizotinib is suggested as a 
promising treatment for unresectable cases with ALK rearrangements. In cases withoutALK rearrangement, 
chemotherapy is an alternative treatment for unresectable tumors. 
Cases report: We report 4 cases of IMT treated in Children Hospital Number 2 since 2018. There was 
one case with mesenteric tumor, one with perineal tumor detected at birth, one with inferior mediastinal 
tumor and one with intestinal tumor. We evaluated ALK expression by immunohistochemistry and ALK 
rearrangement by fluorescence in situ hybridization (FISH) in 3 cases and all negative. Treatments included 
tumor resection or biopsy and chemotherapy with methotrexate (30mg/m2) day 1 and vincristine (1.5mg/
m2) day 1 and 7 in a 3 week cycle together with NSAID or steroid for inflammatory control. There was one 
case with complete response to surgery and chemotherapy; the other 3 cases ended in death due to tumor 
recurrence (3 cases) and metastasis (1 case). 
Conclusions: IMT has a diverse clinical presentation, appears in many different locations, and the 
clinical course can progress quickly with high rate of recurrence after incomplete surgical resection. Surgery 
is the optimal approach, but in those without complete resection and in those with tumor progression, 
tyrosine kinase inhibition should be considered if there is ALK rearrangement. In the absence of ALK 
rearrangement, additional tyrosine kinase rearrangements and other potentially efficacious chemotherapy 
regimens need to be studied for these patients. 
Keywords: Inflammatory myofibroblastic tumor, ALK, mesothelioma
1. Pediatric Department, University of Medicine and Pharmacy 
at Ho Chi Minh City
2. Oncology-Hematology Department, Children Hospital 
Number 2; 
3. Day Surgery Department, Children Hospital Number 2; 
4. Pediatric Surgery Department, University of Medicine and 
Pharmacy at Ho Chi Minh City
- Received: 2/6/2020; Revised: 10/7/2020; 
- Accepted: 4/9/2020 
- Corresponding author: Dao Thi Thanh An 
- Email: daothithanhan@ump.edu.vn; Phone: +84 907053968
Characteristic of inflammatory myofibri oblastic tumor...
Hue Central Hospital
Journal of Clinical Medicine - No. 64/2020 71
I. INTRODUCTION 
Inflammatory myofibroblastic tumor (IMT) is 
a rare type of mesothelioma that can manifest at 
different ages, especially in children and young 
people. About 150-200 cases are recorded annually 
in the United States. The location of the tumor 
varies but is often noted in the lungs, eye sockets, 
and abdominopelvic/retroperitoneal. The main 
treatment for IMT is surgery, but complete surgical 
resection is difficult for patients with invasion 
of adjacent structures or advanced disease. The 
pathology of disease is unknown, but there are many 
factors associated with the formation of IMT such 
as chronic inflammation, autoimmune disease or 
trauma. Specific inflammatory conditions, such as 
IgG4-related disease, are also associated with IMT. 
IMT is diagnosed pathologically using criteria 
established by the World Health Organization 
(WHO). These tumors are characterized by a 
spindle myofibroblastic cell proliferation with 
a lymphoplasmacytic inflammatory infiltrate 
and eosinophils[1]. Fifty percent of IMTs have 
anaplastic lymphoma kinase (ALK) expression 
and overexpress ALK protein. The most common 
mechanism of ALK expression and activation 
involves structural rearrangements in the ALK gene, 
leading to the formation of a chimeric fusion protein. 
Tumors with ALK expression respond partially to 
ALK tyrosine kinase inhibitors (crizotinib) while 
tumors without ALK expression do not respond to 
this agent[2, 3]. ALK-negative IMT may be more 
aggressive with a higher frequency of metastasis 
compared with ALK-positive IMT[4]. 
By next generation sequencing method, 
many different rearrangement genes have been 
discovered. A recent report showed that up to 85% 
of IMTs have kinase fusions, including ALK, ROS1 
or PDGFRβ[5].These data provide a rationale for 
routine molecular profiling to detect therapeutically 
actionable kinase fusions to increase treatment 
opportunities for patients[5]. 
Treatment depends on the tumor location, 
resectability, tumor extension and metastases. 
Surgery is the mainstay treatment option for IMT. 
Other therapies include corticosteroids, NSAID 
anti-inflammatory drugs and immunosuppressive 
drugs to reduce tumor size in addition to radiation 
therapy. Chemotherapy efficacy has been reported 
by some centers when surgery cannot be performed 
due to advanced tumors. Chemotherapy drugs 
including methotrexate (MTX), vinblastine (VBL), 
vincristine, cyclophosphamide, doxorubicin, 
5-fluorouracil, cisplatin, carboplatin, paclitaxel, 
ifosfamide and etoposide have been reported[6]. Tao 
et al.[3] reported successful treatment of a 14-year-
old girl with retroperitoneal IMT with surgical 
treatment combined with 6 cycles of methotrexate 
20mg/m2 and cisplatin each month in combination 
with low dose diclofenac sodium. Tumors with 
ALK expression have been successfully treated 
with crizotinib, a tyrosine kinase ALK inhibitor[3, 
7]. As reported by the European soft tissue group, 
for ALK-negative cases, the response rate to 
chemotherapy is 80% (8/10) including vinblastine-
methotrexate while in the group of ALK positive, 
the response to ALK inhibition is 100% (5/5) cases. 
They concluded that there was similar prognosis for 
patients with and without ALK expression. 
II. CASE SERIES
Since 2018, Oncology-Hematology Department 
of Children Hospital 2 at Ho Chi Minh City 
recorded 4 cases diagnosed with IMT with various 
clinical manifestations: one case of enlarged 
mesothelioma, one with tumor in the perineal 
region, one in the anterior mediastinum and one in 
the small intestine. In these 4 cases, 3 were tested 
for immunohistochemistry or recombinant ALK 
gene but all three cases were negative. Three of 
the 4 cases relapsed locally and progressed after 
surgery and resulted in death despite treatment 
with methotrexate vincristine and NSAID or 
1. Pediatric Department, University of Medicine and Pharmacy 
at Ho Chi Minh City
2. Oncology-Hematology Department, Children Hospital 
Number 2; 
3. Day Surgery Department, Children Hospital Number 2; 
4. Pediatric Surgery Department, University of Medicine and 
Pharmacy at Ho Chi Minh City
- Received: 2/6/2020; Revised: 10/7/2020; 
- Accepted: 4/9/2020 
- Corresponding author: Dao Thi Thanh An 
- Email: daothithanhan@ump.edu.vn; Phone: +84 907053968
Bệnh viện Trung ương Huế 
72 Journal of Clinical Medicine - No. 64/2020
corticosteroid anti-inflammatory drugs; one case 
responded well to surgery and chemotherapy, 
currently under observation.
Clinical case 1: A 14-year-old girl patient 
hospitalized for abdominal pain, ultrasound and 
CT scan noted mesenteric tumor, size 10x10x15cm 
characterized by calcification, necrosis, increased 
vascular hyperplasia and adhesion to small intestine. 
A complete blood count indicated anemia, increased 
inflammatory response manifested by increased 
ferritin, fibrinogen, and increased platelets; AFP, 
bHCG, CEA tests were within normal limits. The 
patient had the tumor resected together with 15cm 
of jejunum and transverse colon. There was some 
part of peritoneal with small tumors could not be 
resected. Peritoneal wash for cell block was negative. 
Pathology revealed that the tumor tissue consisted 
of many cells with long nucleus, hypercellularity, 
small, long, thin cytoplasm, forming clusters, 
having many blood vessels and inflammatory cells 
infiltration. Immunohistochemistry of CD117 (-), 
Ki67 (+) 2%, Vimentin (+), Actin (+), DOG-1 (-), 
ALK (-). Fluorescence in situ hybridization assay 
was negative for ALK rearrangement. After surgery, 
the patient was clinically monitored. Three month 
later after presenting with recurrence with peritoneal 
and pleural effusion, the patient commenced 
chemotherapy with methotrexate and vincristine, 
anti-inflammatory (NSAIDs) but progressed and 
died at home after 3 cycles of chemotherapy.
a, b) CT scans shows large mesenteric 
tumor with calcification, necrosis, vascular 
proliferation.
c) Negative for ALK rearrangement in the 
fluorescent in situ hybridization (FISH) test .
d) Histology noted that the tumor tissue 
consists of many cells with long nuclei, 
hypercellularity, small, long, thin cytoplasm, 
forming clusters, having many blood vessels 
and inflammatory cells infiltration. 
a) Image of a perineal tumor.
b) CT scan shows an image of the solid tumor in 
perineal region, d = 6.1cm, uncleard margin. 
c) Histology noted the tumor tissue included spindle 
cell hyperplasia, including intercellular fibroblasts 
with angiogenesis, and acute inflammatory cell 
proliferation, eosinophils and lymphocytes.
d) Negative for ALK rearrangement.
 Figure 1: Mesenteric inflammatory
myofibroblastic tumor
Clinical case 2: A 4-month-old girl hospitalized 
with a perineal tumor detected after birth, histology 
noted that tumor tissue including spindle cell prolif-
eration composed of fibroblasts with angiogenesis, 
and acute inflammatory cells, eosinophils, lym-
phocytes; immunohistochemistry showed Ki67 (+) 
10%, CD31 (-), Actin (-), Myogenin (-) , Desmin 
(-); no rearrangement of ALK on FISH (Figure 2). 
Patient underwent complete surgery and was treated 
with 6 cycles of methotrexate and vincristine. She 
had a complete response and is stable after 8 months 
of treatment.
Figure 2: Perineal inflammatory myofibroblastic tumor.
Characteristic of inflammatory myofibri oblastic tumor...
Hue Central Hospital
Journal of Clinical Medicine - No. 64/2020 73
Clinical case 3: An 11-year-old boy with a large 
neck tumor who had a first biopsy diagnosed with 
fibromatosis, he was followed up 3 months after 
biopsy but the tumor progressed quickly, the patient 
was admitted to the hospital with respiratory distress, 
CT scan recorded large size anterior mediastinal 
mass, spreading to left neck. The tumor surrounded 
the left subclavian artery, compressed the left 
internal jugular vein and left brachiocephalic vein. 
There were thromboses in the right internal jugular 
vein and left subclavian vein causing left pleural 
effusion. Secondary tumor biopsy was performed 
and histology recorded spindle cells arranged 
in bundles in different directions, infiltrated 
with many inflammatory cells and mast cells. 
Immunohistochemistry showed Actin (+), Ki67 (-), 
CD34 (-), S100 (-). The tumor was unresectable so 
chemotherapy was initiated including methotreaxate 
and vincristine after biopsy. Unfortunately, the 
respiratory failure progressed, he needed prolonged 
ventilatory support, and died after 3 weeks in the 
intensive care unit. 
Clinical case 4: A 14-year-old boy presented 
with abdominal pain; ultrasound and CT scan 
reported an intestinal tumor. He underwent surgery 
to resect the tumor (size=30x15x10 cm) in the 
intestine including appendix, lymph nodes of 
accending colon. Histology noted multiple degree 
of spindle cells proliferation forming in bundles, 
mostly fibroblasts, many cytoplasm, bright nuclei, 
infiltrated by inflammation cells and angiogenesis 
on tumor tissues and resection margin; the lymph 
nodes had no tumor cell. Immunohistochemistry 
showed actin (+), blood vessels, ALK (-). Patient 
received 6-cycle methotrexate and vincristine, 
but the tumor recurred quickly after surgery and 
chemotherapy, and had metastatic nodules in right 
lung. He died after 2 months of follow up. 
Figure 3: Histology of anterior mediastinal 
inflammatory myofibroblastic tumor. 
a) Photo of intestinal tumors after surgery.
b) Histology showed many spindle cells, 
numerous cytoplasm, bright nuclei, infiltrated by 
many inflammatory cells and angiogenesis. 
Figure 4: Intestinal inflammatory
myofibroblastic tumor
 Table 1: Patient characteristics and ALK status
Characteristics Sex/Age Clinical presentation 
Primary 
Site 
Immunohisto-
chemistry 
ALK rearrangement/ 
FISH 
PT 1 F, 14 years
Abdominal 
pain, anemia, 
fatigue 
Messentery 
CD117 (-), Ki67 (+) 
2%, Vimentin (+), 
Actin (+), DOG-1 
(-), ALK (-)
Negative 
PT 2 F, 4 months 
Perineal tumor 
detected after 
birth 
Perineum 
Ki67 (+) 10%, 
CD31 (-), Actin 
(-), Myogenin (-), 
Desmin (-) ALK (-)
Negative 
PT 3 M, 11 years
Dyspnea, 
fatigue 
Anterior 
mediastinum
Actin(+), Ki67 (-), 
CD34 (-), S100 (-). 
NA
PT 4 M, 14 years Abdominal pain 
Small 
intestine Actin (+), ALK (-) Negative 
NA: not applicable 
Bệnh viện Trung ương Huế 
74 Journal of Clinical Medicine - No. 64/2020
Table 2: Patient laboratory findings 
Characteristics PT 1 PT 2 PT 3 PT 4 Reference
WBC 20.9 18.8 12.8 16.3 4.0-10.0 K/uL
Neu 15.4 9.5 7.4 12.1 2.0-6.9 K/uL
Lym 3.8 8.7 3.9 2.8 0.6-3.4 K/uL
Mono 1.0 0.5 0.9 1.2 0.0-0.9 K/uL
Hgb 8.4 7.8 8.9 10.4 125-160 g/L
MCV 69 72 73 75 80-98 Fl
PLT 1030 415 365 264 150-450 K/uL
Ferritin 4146 319 NA NA 15-120 µg/L
Fibrinogen 11.5 3.2 5.8 5.4 2-4 g/L
LDH 124 172 264 222 420-750 U/L
NA: not applicable
Table 3: Treatment and Outcome 
Charac-
teristic Surgery
Anti-Inflam-
mation Chemotherapy Progression Outcome
PT 1 Incomplete resection NSAID Vincristine+Methotrexate Recurrence Dead 
PT 2 Incomplete resection No Vincristine+Methotrexate
Complete re-
sponse Alive 
PT 3 Biopsy Steroid Vincristine+Methotrexate Progression Dead
PT 4 Incomplete resection Steroid Vincristine+Methotrexate
R e c u r r e n c e , 
lung metastasis Dead
I. DISCUSSION
Inflammatory myofibroblastic tumor has 
intermediate malignant potential because its clinical 
course is relatively indolent with low risk of distant 
metastasis. ALK is a potential therapeutic target for 
IMT, however in our small series the expression 
of ALK was negative in all 3 cases tested. In our 
case series, one case with perineal tumor detected 
at birth and completed resected at 4 months of 
age had a good response to definitive surgical 
treatment, whereas the other three cases led to death 
because of tumor recurrence and progression.The 
clinical manifestations of IMT are very diverse, 
with it appearing in many different locations, and 
the clinical course can progress quickly with high 
rate of recurrence after surgery. All 3 cases tested 
in our center showed negative ALK expression by 
immunohistochemistry or rearrangement by FISH. 
Three of four patients had recurrent tumors, one 
with lung metastasis. Patient 2 who had complete 
response to treatment had tumor detection from 
birth and was treated at 4 months of age. The slow 
progression of this tumor may indicate that its 
biology is more benign than the other three cases. 
Patient 1 had markedly increased inflammatory 
response markers such as very high ferritin, high 
fibrinogen and high platelet count during follow-up 
and this may be a risk for tumor progression and 
poor response to chemotherapy. The high death rate 
in our small cohort may be because patients came 
in with advanced stage disease and none had ALK 
expression allowing for treatment with a targeted 
molecular agent. Although chemotherapy efficacy 
Characteristic of inflammatory myofibri oblastic tumor...
Hue Central Hospital
Journal of Clinical Medicine - No. 64/2020 75
has been reported, it is only in isolated case reports. 
We found that chemotherapy with methotrexate 
and vincristine was ineffective in controlling tumor 
progression in our cases, with rapid recurrence 
and subsequent progression. This may relate to the 
advanced stage of disease at presentation which is 
difficult for complete resection and the difficulty of 
access to vinblastin in our center. Other potential 
molecular targets should be sought to better 
understand the biology of IMT and potentially offer 
additional therapeutic options. 
II. CONCLUSIONS
Inflammatory myofibroblastic tumor has a diverse 
clinical presentation, appears in many different 
locations, and the clinical course can progress quickly 
and high rate of relapse after surgery. The main 
treatment is surgery, with prevention or treatment of 
disease progression with an ALK inhibiting tyrosine 
kinase if there is ALK rearrangement. In cases of 
unresectable tumors and cases negative for ALK, 
other targeted molecular agents and chemotherapy 
drugs need to investigated for these patients.
REFERENCES
1. Coindre, J.M., [New WHO classification of 
tumours of soft tissue and bone]. Ann Pathol, 
2012. 32 (5 Suppl): p. S115-6.
2. Nagumo, Y., et al., Neoadjuvant crizotinib in 
ALK-rearranged inflammatory myofibroblastic 
tumor of the urinary bladder: A case report. Int J 
Surg Case Rep, 2018. 48: p. 1-4.
3. Butrynski, J.E., et al., Crizotinib in ALK-
rearranged inflammatory myofibroblastic tumor. 
N Engl J Med, 2010. 363(18): p. 1727-33.
4. Coffin, C.M., J.L. Hornick, and C.D. Fletcher, 
Inflammatory myofibroblastic tumor: 
comparison of clinicopathologic, histologic, and 
immunohistochemical features including ALK 
expression in atypical and aggressive cases. Am 
J Surg Pathol, 2007. 31(4): p. 509-20.
5. Lovly, C.M., et al., Inflammatory myofibroblastic 
tumors harbor multiple potentially actionable kinase 
fusions. Cancer Discov, 2014. 4(8): p. 889-95.
6. Tao, Y.L., et al., Inflammatory myofibroblastic 
tumor successfully treated with chemotherapy 
and nonsteroidals: a case report. World J 
Gastroenterol, 2012. 18(47): p. 7100-3.
7. Gaudichon, J., et al., Complete and Repeated 
Response of a Metastatic ALK-rearranged 
Inflammatory Myofibroblastic Tumor to 
Crizotinib in a Teenage Girl. J Pediatr Hematol 
Oncol, 2016. 38(4): p. 308-11.