Inflammatory myofibroblastic tumor

Cessna MH, Zhou H, Sanger WG, et al. Expression of ALKl and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics A study of 135 cases. Mod Pathol. 2002 15 931-938. 

Sigel JE, Smith TA, Reith JD, et al. Immunohistochemical analysis of anaplastic lymphoma kinase expression in deep soft tissue calcifying fibrous pseudotumor evidence of a late sclerosing stage of inflammatory myofibroblastic tumor Ann Diagn Pathol. 2001 5 10-14. 

Coffin CM, Watterson J, Priest JR, et al. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor) A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol. 1995 19 859-872. 

Freeman A, Geddes N, Munson P, et al. Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumors of the bladder A preliminary clinicopathologic study of nine cases and review of the literature. Mod Pathol. 2004 17 765-771. 

CIST, gastrointestinal stromal tumor IMT, Inflammatory myofibroblastic tumor N, negative PR, progesterone receptor S, sometimes positive SFT, solitary fibrous tumor SMA, smooth muscle actin SS, stromal sarcoma +, almost always positive. 

Anaplastic lymphoma kinase (ALK) is a cytoplasmic membrane tyrosine kinase receptor expressed in anaplastic large cell lymphoma. ALK expression has been detected in about two thirds of inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor. 

We limit our discussion here to two of the benign mim-ickers of bladder tumors nephrogenic adenoma as a mimic of both urothelial carcinoma and adenocarcinoma and inflammatory myofibroblastic tumor (IMT) as mimic of sarcomatoid carcinoma or sarcomas. 

An inflammatory myofibroblastic tumor (IMT) of the bladder may arise either spontaneously or as a result of a prior instrumentation of the bladder. IMTs are benign mesenchymal neoplasms composed of a proliferation of relatively monotonous myofibroblastic cells (typical tissue culture appearance) in a richly vascularized background with red blood cell extravasation and lym-phoplasmacytic inflammatory infiltrate. Mitotic activity ranges from absent to brisk. Abnormal mitotic figures... 

FIGURE 16.29 Interphase fluorescence in situ hybridization analysis for ALK-1 gene in inflammatory myofibroblastic tumor using split-apart probes. The presence of a set of one green and one red signal in addition to a juxtaposed red-green (yellow overlap) set indicates a rearrangement in one of the two ALK-1 alleles. 

FIGURE 16.30 Inflammatory myofibroblastic tumor of the urinary bladder (A and B). Positive ALK-1 staining (C). 

ALK, anaplastic lymphoma kinase EMA, epithelial membrane antigen IMT, inflammatory myofibroblastic tumor MSA, muscle-specific actin +, almost always positive S, sometimes positive N, negative. 

Cook JR, Dehner LP, Collins MH, et al. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor a comparative immunohistochemical study. Am J Surg Pathol. 2001 25 1364. 

Tsuzuki T, Magi-Galluzzi C, Epstein JI. ALK-1 expression in inflammatory myofibroblastic tumor of the urinary bladder. Am J Surg Pathol. 2004 28 1609. 

Sukov WR, Cheville JC, Carlson AW, et al. Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell lesions of the urinary bladder. Mod Pathol. 2007 20 592. 

This is a very rare, possibly benign uterine tumor that is characterized by a cytologically bland and largely mitot-ically inactive proliferation of spindle cells in a myxoid matrix. The main differential diagnostic considerations include myxoid leiomyoma and leiomyosarcoma and endometrial stromal neoplasm with myxoid stroma. All inflammatory myofibroblastic tumors reported in the largest series were ALK-positive, which is similar to what has been described to occur in other sites. " All uterine mesenchymal neoplasms studied were ALK-negative, including smooth muscle and endometrial stromal tumors and carcinosarcomas. 

Tropomyosin 3 (TMP3, also known as TRK or NEMl) gene located on chromosome lq25 encoding a 284 amino acid protein with coiled coil structure involved in the calcium-dependent actin-myosin interaction. This gene is the fusion partner of the ALK gene in the t(l 2)(q25 p23) translocation. This translocation seems to be the most common translocation associated with the inflammatory myofibroblastic tumor but it is also detected in other tumors such as the anaplastic large cell lymphoma discussed in a later section. 

The detection of the above-mentioned chromosomal abnormalities can support the diagnosis of inflammatory myofibroblastic tumor, especially in atypical tumor locations or doubtful immunohistochemical profile. The association with HHV-8 vims is a further interesting aspect discussed in a later chapter. 

In conclusion, the atypical activation of ALK signaling pathways caused by different cytogenetic abnormalities appears to have an etiologic significance in the initiation of the malignant transformation of ALCL and few other tumors such as inflammatory myofibroblastic tumor. 

K. et al. (2000) TMP3-ALK and TMP4-ALK oncogenes in inflammatory myofibroblastic tumors. Am J Pathol, 157, 377-384. 

Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. Am J Pathol, 159, 411 15. 

Gomez-Roman, J.J., Ocejo-Viyals, G., Sanchez-Velasco, P. et al. (2000) Presence of human herpisvirus-8 DNA sequences and overexpression of human IL-6 and cydin D1 in inflammatory myofibroblastic tumor (inflammatory pseudotumor). Lab Invest, 80, 1121-1126. 

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