Discussion
Our cohort represents a group of children with IMFT with varied
presentations. A low-dose oral out-patient based combination
chemotherapy, including prednisolone, 6-mercaptopurine, methotrexate,
and celecoxib, was well-tolerated and showed good efficacy. In children
with abdominal disease, where complete surgical excision was not
possible, recurrence was noted, which responded to targeted therapy with
crizotinib.
Diagnosis can be challenging, and a high index of suspicion is
essential. IMFTs are characterized by a variably cellular spindle cell
proliferation in a myxoid to collagenous stroma with a prominent
inflammatory infiltrate composed primarily of plasma cells and
lymphocytes, with occasional eosinophils and neutrophils (4, 6). The
absence of anaplasia, lack of mitotic figures, and the inflammatory
background differentiate IMFT from soft tissue sarcomas. IHC may not be
definitive because of variable expression and lack of specificity of
these markers such as smooth muscle actin, muscle-specific actin, and
vimentin. Rearrangements involving the ALK locus on chromosome 2p23 have
been documented in approximately 50% of IMFTs (7, 8).
Surgery has been known to be the mainstay of treatment. Surgical
resection should be recommended for all lesions if not limited by
anatomic location or morbidity. Recurrence is rare following complete
excision of a solitary lesion, depending upon the anatomical site, from
2% for tumors confined to the lung to 25% for extrapulmonary lesions
(9, 10). We performed surgery for 3 of our cases (child#1, 2, and 4).
In child #3 and 5, surgery was not offered because of the tumor’s
difficult anatomic location.
Various adjuvant chemotherapy regimens have been used in the past with
limited efficacy (3, 9, 11). Oral methotrexate and 6-MP have been found
to be potentially active chemotherapeutic agents. Several groups have
published encouraging results with steroids and non-steroidal
anti-inflammatory agents (NSAIDS) with or without concomitant
chemotherapy (12, 13). Applebaum et al . described the inhibitory
effect of NSAIDs through disruption of angiogenesis by interfering with
vascular endothelial growth factor signaling via cyclooxygenase 2
(COX-2) inhibition (14).
Crizotinib is a small-molecule tyrosine kinase inhibitor targeting
several kinases, including ALK and MET. Recent studies have shown the
efficacy of crizotinib in the management of ALK-positive IMFTs (15, 16,
17). In the Children’s Oncology Group study, an overall response rate of
86% was noted with crizotinib in refractory IMFTs, with the most common
adverse effect being neutropenia (16).
IMFT requires a multidisciplinary team of pediatric surgeons,
pathologists, nursing, and oncologists. Long term follow-up and
prolonged therapy are essential to sustain remission. Maximal safe
resection followed by oral chemotherapy with low-dose prednisolone,
methotrexate, 6-MP, and celecoxib helps achieve remission in two-thirds
of the children. Crizotinib is a useful salvage agent in recurrent
tumors that are ALK-positive.
Acknowledgments: We would like to acknowledge the contribution of the
histopathology department in the management of these children
Conflicts of interest: none
Funding: none