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PATHOLOGY
Inflammatory
Myofibroblastic Tumors of the Urinary Tract: A Clinicopathologic Study
of 46 Cases, Including a Malignant Example Inflammatory Fibrosarcoma and
a Subset Associated With High-Grade Urothelial Carcinoma
Montgomery EA, Shuster DD, Burkart AL, Esteban JM, Sgrignoli A, Elwood
L, Vaughn DJ, Griffin CA, Epstein JI
Department of Pathology, Johns Hopkins Hospital, Baltimore, USA
Am J Surg Pathol. 2006; 30: 1502-12
- Inflammatory
myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative
spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous
fibromyxoid tumor, is rare and in the past was believed to reflect diverse
entities. We reviewed a series of 46 IMTs arising in the ureter, bladder,
and prostate, derived primarily from a large consultation practice.
There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions
were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation
in 8 cases. Morphology was similar to that previously described for
IMT occurring in this region, with the exception of 1 case that focally
appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%).
Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was
seen in 14 (30%) cases. Invasion of the muscularis propria was documented
in 19 (41%). By immunohistochemistry (IHC), lesions at least focally
expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34,
73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin
(15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells),
p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13,
15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected
by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases,
including 2 with prior instrumentation; 13/18 (72%) showed agreement
between FISH ALK results and ALK protein results by IHC. Most bladder
IMTs were managed locally, but partial cystectomy was performed as the
initial management in 7 cases and cystectomy in 1 (1 IMT was initially
misinterpreted as carcinoma, 1 IMT was found incidentally as a separate
lesion in a cystectomy specimen performed for urothelial carcinoma).
Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median
24). There were 10 patients with recurrences (2 with 2 recurrences).
Recurrences were unassociated with muscle invasion or with ALK alterations.
In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded
(1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade
invasive urothelial carcinoma accompanied with separate fragments of
IMT. Even on re-review the IMT in these 2 cases were morphologically
indistinguishable from other cases of IMT, with FISH demonstrating ALK
alterations in the IMT areas in one of them. Both these patients died
of their carcinomas. Lastly, there was 1 tumor with many morphological
features of IMT and an ALK rearrangement, yet overtly sarcomatous. This
case arose postirradiation for prostate cancer 4 years before the development
of the lesion, with tumor recurrence at 4 months and death from intra-abdominal
metastatic disease at 9 months. In summary, urinary tract IMTs are rare
and share many features with counterparts in other sites, displaying
similar morphology and immunogenotypic features whether de novo or postinstrumentation.
Typical IMTs can be locally aggressive, sometimes requiring radical
surgical resection, but none of our typical cases metastasized, although
they can rarely arise contemporaneously with sarcomatoid urothelial
carcinomas. For these reasons, close follow-up is warranted.
- Editorial
Comment
It is controversial in the literature whether inflammatory myofibroblastic
tumor of the urinary tract is an inflammatory or a neoplastic lesion.
This is the reason for the vast list of synonyms: reactive pseudosarcomatous
response, postoperative spindle cell nodule, inflammatory pseudotumor,
nodular fasciitis, pseudomalignant spindle cell proliferation, pseudosarcomatous
myofibroblastic proliferation, pseudosarcomatous myofibroblastic tumor,
and inflammatory myofibroblatic tumor.
The lesion mimics both sarcomas and spindled carcinomas, the latter
compounded by their expression of various cytokeratins (1). Considering
that the lesion in the urinary tract has been benign in almost all series
it would be similar to nodular fasciitis elsewhere. However, it differs
by nodular fasciitis in its capacity to infiltrate deeply into the detrusor
muscle (2).
The identification of ALK alterations in bladder lesions suggests that,
despite the frequent similarity to nodular fasciitis, inflammatory myofibroblastic
tumor is neoplastic (3). There is a clonal aberration typically involving
chromosome 2p. This results in rearrangement of the ALK gene which codifies
a receptor of tyrosine-kinase and hence over-expression of ALK-1 protein.
This over-expression of the ALK protein is also seen in anaplastic large
cell lymphomas.
References
1. Freeman A, Geddes N, Munson P, Joseph J, Ramani P, Sandison A, et al.:
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. 2004; 17:
765-71.
2. Billis A: Weekly conference with the residents. Case 21. Available:
http://www.fcm.unicamp.br/deptos/anatomia/casosdeuro/casosdeuroentrada.html.
3. Tsuzuki T, Magi-Galluzzi C, Epstein JI: ALK-1 expression in inflammatory
myofibroblastic tumor of the urinary bladder. Am J Surg Pathol. 2004;
28: 1609-14.
Dr.
Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, Sao Paulo, Brazil |