Soft Tissue Tumors in Children and Adolescents:
A Morphologic Pattern Oriented Approach with Molecular and Genetic Correlations
Section 7 -
Inflammatory Myofibroblastic Tumor
Cheryl M. Coffin, M.D.
David M. Parham, M.D.
A 7-year old girl with anemia and thrombocytosis was found to have a large abdominopelvic mass.
Laboratory abnormalities included anemia, thrombocytosis, elevated erythrocyte sedimentation rate, and
elevated C-reactive protein. She underwent resection of an 11 cm tan, whorled mass with focal necrosis.
The laboratory abnormalities resolved after surgery.
Discussion and Differential Diagnosis:
This case represents an example of inflammatory myofibroblastic tumor with thrombocytosis,
megakaryocytic hyperplasia, and a unique chromosomal translocation with ALK
rearrangement. The points for discussion are the clinicopathologic and molecular genetic features of
IMT, its classification, and differential diagnosis.
The 300 g, 11.0 cm, tan, whorled mass had a predominantly spindled inflammatory cellular pattern with
unusual histologic features of coagulative necrosis, foci of high cellularity with a herringbone pattern,
and clusters of multinucleated giant cells within the tumor. Immunohistochemical staining revealed
cytoplasmic reactivity for smooth muscle actin and ALK1 in the spindle cells and strong membranous
cytoplasmic CD61 reactivity in the multinucleated giant cells, indicative of megakaryocytic
differentiation. The cytogenetic analysis revealed a complex tumor karyotype including a translocation
In the current WHO Classification, IMT is defined as a distinctive neoplasm of intermediate grade with
a low risk of metastasis. It is composed of myofibroblastic spindle cells accompanied by an inflammatory
infiltrate of plasma cells, lymphocytes, and eosinophils. Although primarily a visceral and soft tissue
tumor of children and young adults, the age range extends throughout life and the abdominopelvic region
is a common site. Up to one-third of patients experience the clinical syndrome of fever, growth failure,
malaise, weight loss, anemia, thrombocytosis, polyclonal hyperglobulinemia, and elevated erythrocyte
sedimentation rate. A variety of cytogenetic and molecular genetic abnormalities have been reported in
IMT and these have in common clonal cytogenetic arrangements that involve the ALK-receptor tyrosine kinase gene at chromosome 2p23. Immunohistochemical
reactivity for ALK-1 correlates well with the presence of ALK gene
rearrangements detectable by fluorescent in situ hybridization, cytogenetics, or RT-PCR. Fusion
oncogenes with ALK include tropomyosin 3, tropomyosin 4, clathrin, and other
genes. Local recurrence develops in 25% of cases, fewer than 5% metastasize to distant sites, and rare
cases undergo histologic evolution to a high-grade spindle cell or round cell neoplasm. At present
surgery is the principal treatment, although regression and response to various pharmacologic agents have
been reported in individual cases. Reliable prognostic indicators remain elusive; absence of an ALK
rearrangement may portend a higher risk of metastasis.
The differential diagnosis of inflammatory myofibroblastic tumor includes infectious and reactive
processes, dendritic cell neoplasms, lymphoma, fibromatoses, nodular fasciitis, fibrous histiocytoma,
smooth muscle neoplasms, sarcomatoid carcinoma, melanoma, rhabdomyosarcoma, and other spindle cell
neoplasms. Distinction between IMT and these lesions depends in part on the histologic appearance of
IMT, which can have a variety of histologic patterns including a myxoid vascular pattern, a compact
inflammatory fascicular pattern, and a collagenized scar-like pattern. Usually histology and
immunohistochemistry are sufficient to establish the diagnosis. ALK abnormalities are found in
approximately one-half to two-thirds of cases, but may also be seen in a anaplastic large cell lymphoma
and rhabdomyosarcoma. Inflammatory pseudotumor of lymph nodes and spleen is a separate entity from IMT.
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