Inflammatory myofibroblastic tumour

The presence of chromosomal abnormalities involving the ALK gene at 2p23, and associating it with either of the tropomyosin genes (TPM3 or TPM4), or less commonly with the clathrin heavy chain (CLTC), cysteinyl-tRNA synthetase or Ran-binding protein 2⁴, to produce a protein fusion product, indicates that this subset of inflammatory pseudotumours are true neoplasms. Some consider inflammatory fibrosarcoma to be synonymous with inflammatory myofibroblastic tumour^1,9.

Cases occurring in lymph nodes and the spleen are reported as having genomic-encoded EBV RNA⁴.

Synonyms

Inflammatory pseudotumour, inflammatory fibromyxoid tumour, postoperative spindle cell nodule, plasma cell granuloma, intra-abdominal myxoid hamartoma¹³.

Clinical features

Most patients are young (average 10 years). They may have a fever¹² and weight loss. Haematological features include anaemia¹², thrombocytosis¹², raised ESR and raised gamma globulins. The tumour forms a mass, which is most commonly located in the lungs, but may occur in soft tissues of the head and neck, mesentery, omentum, retroperitoneum, liver or bladder, less often in soft tissues of the trunk or extremities.

Histopathology

These tumours consist of proliferating spindle cell myofibroblasts, admixed with a lymphoplasmacytic infiltrate.

Three histological patterns have been described:

1. myxoid-vascular, resembling nodular fasciitis: cells are widely separated in a myxoid stroma. There is a prominent network of small dilated vessels.

2. compact spindle cell, resembling GIST, fibrohistiocytoma or a smooth muscle tumour. The pattern is storiform or fascicular.

3. hypocellular fibrous, resembling a scar or fibromatosis. Where this pattern predominates, ALK-11 is less likely to be positive¹.

Round cell transformation, in which the tumour acquires a component, or is overgrown, by polygonal cells (ganglion-like) with abundant eosinophilic cytoplasm, large round nuclei, prominent nucleoli, is associated with more aggressive behavior⁸.

Immunohistochemistry

The staining pattern is usually diffusely cytoplasmic but may be granular (associated with the presence of a fusion between the clathrin heavy chain gene and ALK: the granularity is presumably due to the incorporation of the fusion product into the polyhedral coat of clathrin-coated vesicles) and rarely there is nuclear membrane staining¹.

Site of inflammatory myofibroblastic tumour:	ALK-11
Gastrointestinal/mesenteric	12/201
Peritoneum/omentum	7/71
Larynx/trachea	3/41
Lung	6/131
Soft tissue	2/51
Bladder	3/41
Lymph node	0/31
Breast	0/11
Liver	1/11
Oropharynx	1/11
Spleen	0/11
Testis	1/11
Uterus	1/11
Unknown	7/111
Total	44/731 (60%)
for comparison:
nodular fasciitis	0/201
desmoid fibromatosis	0/151
GIST	0/151
Leiomyoma	negative (ALK-1)2
myofibrosarcoma	negative (ALK-1)2
alveolar rhabdomyosarcoma	20% (ALK-1)2
malignant peripheral nerve sheath tumour	40% (ALK-1)2

	bax	24/248
	bcl-2	9/248
	p53	2/248
	c-myc	0/248

Cytogenetics

A proportion of cases show chromosomal translocations^11,13, are aneuploid⁸ or hyperploid⁶. There is commonly a translocation involving the ALK gene at 2p23⁷.

Differential diagnosis

3		Cytokeratin	SMA	Desmin	Calponin	Caldesmon	MyoD1	S-100	ALK
Inflammatory myofibroblastic tumour3	Pushing margins, mildly pleomorphic, myxoid stroma, inflammatory infiltrate	20-40% of cases positive	>90% of cases positive	positive in up to 70% of cases	usually positive	usually positive	negative	negative	usually positive
Spindle cell carcinoma3	Surface urothelium may show atypia. Pleomorphism is marked. Margins are infiltrative.	positive	focal positivity in less than 25% of cases	focal positivity in less than 25% of cases	negative	negative	negative	negative	negative
Leiomyosarcoma3	Parallel fascicles, cigar-shaped nuclei, paranuclear vacuoles	up to 30% of cases positive	positive	positive	positive	positive	negative	negative	negative
Neurofibroma3	Polypoidal or plexiform, wavy nuclei	negative	negative	negative	negative	negative	negative	positive	negative
Rhabdomyosarcoma3,5	Bladder, children and adolescents, uniform small round blue cells	negative	usually negative	positive	negative	negative	positive	negative	positive in up to 20% of cases
GIST
non-neoplastic, reactive inflammatory pseudotumour.
nodular fasciitis
desmoid fibromatosis
calcifying fibrous (pseudo)tumour
inflammatory fibroid polyp of the gastrointestinal tract
follicular dendritic cell tumour
Hodgkin lymphoma10

Prognosis

A minority of tumours recur or, rarely, metastasis⁶ . This aggressive behavior is commonly associated with round cell transformation.

References

¹ Cook, J. R., Dehner, L. P., Collins, M. H., Ma, Z., Morris, S. W., Coffin, C. M., Hill, D. A. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol 2001;25:1364-1371.

² Coffin CM, Cessna MH, Perkins S et al. Expression of ALK1 and p80 in inflammatory myofibroblastic tumour (IMT) and its mimics: a study of 135 cases [abstract] Mod Pathol 2001;14:10.

³ Freeman, A., N. Geddes, et al. (2004). "Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature." Mod Pathol 17(7): 765-71.

⁴ Dehner, L. P. (2004). "Inflammatory myofibroblastic tumor: the continued definition of one type of so-called inflammatory pseudotumor." Am J Surg Pathol 28(12): 1652-4.

⁵ Coffin CM, Humphrey PA,Dehner LP Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey. Semin Diagn Pathol 1998; 15:85-101

⁶ Biselli R, Ferlini C, Fattorossi A, et al. Inflammatory myofibroblastic tumor (inflammatory pseudotumor): DNA flow cytometric analysis of nine pediatric cases. Cancer 1996; 77:778-84

⁷ Griffin CA, Hawkins AL, Dvorak C, et al. Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res 1999; 59:2776-80

⁸ Hussong JW, Brown M, Perkins SL, et al. Comparison of DNA ploidy, histologic, and immunohistochemical findings with clinical outcome in inflammatory myofibroblastic tumors. Mod Pathol 1999; 12:279-86

⁹ Meis-Kindblom JM, Kjellstrom C,Kindblom LG Inflammatory fibrosarcoma: update, reappraisal, and perspective on its place in the spectrum of inflammatory myofibroblastic tumors. Semin Diagn Pathol 1998; 15:133-43

¹⁰ Ramachandra S, Hollowood K, Bisceglia M, et al. Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases. Histopathology 1995; 27:313-23

¹¹ Sciot R, Dal Cin P, Fletcher CD, et al. Inflammatory myofibroblastic tumor of bone: report of two cases with evidence of clonal chromosomal changes. Am J Surg Pathol 1997; 21:1166-72

¹² Souid AK, Ziemba MC, Dubansky AS, et al. Inflammatory myofibroblastic tumor in children. Cancer 1993; 72:2042-8

¹³ Su LD, Atayde-Perez A, Sheldon S, et al. Inflammatory myofibroblastic tumor: cytogenetic evidence supporting clonal origin. Mod Pathol 1998; 11:364-8

This page last revised 14.5.2005.

©SMUHT/PW Bishop