Low-grade myofibroblastic proliferations of the urinary bladder.
BACKGROUND AND AIMSIn human pathology, mesenchymal fibroblastic/myofibroblastic spindle cell proliferations constitute an exceedingly broad and heterogeneous category of disorders, ranging from indolent lesions to highly aggressive neoplasms. In this setting, and especially when dealing with reactive and low-grade lesions, the differential diagnosis is often challenging. (1)
In 1980, Roth (2) reported a particular spindle cell proliferation arising in the urinary bladder of a 32-year old woman. This lesion shared several similarities with nodular fasciitis, so it was classified as a reactive proliferation because of the absence of malignant epithelial elements, its benign clinical course, and the patient's well-known history of chronic cystitis. (2) Four years after the Roth (2) initial description, Proppe et al (3) reported on 8 cases of similar spindle cell lesions that occurred 5 weeks to 3 months after genitourinary tract interventions. These benign reactive lesions resembling a sarcoma were called postoperative spindle cell nodules (PSCN). (3) Later on, several authors reportedcases of PSCN that had occurred up to 15 months (usually about 3 months) after urinary bladder surgery or instrumentation. (4-6)
Over time, these myofibroblastic proliferations have had a number of designations, such as inflammatory pseudotumor, inflammatory pseudosarcomatous fibromyxoid tumor, pseudosarcomatous myofibroblastic tumor, fibromyxoid pseudotumor, plasma cell granuloma, plasma cell pseudotumor, and xanthomatous pseudotumour. (6,7) Although most of the abovementioned terms are now considered outdated, the nosology and definition of these lesions are still a matter of debate. Inflammatory myofibroblastic tumor (IMT) of the urinary bladder is probably still the most frequent designation (8-19); however, some authors prefer the term pseudosarcomatous myofibroblastic proliferation (PMP) for a fraction of these myofibroblastic proliferations. These authors believe that, both morphologically and biologically, there are sufficient reasons to distinguish IMT and PMP. In addition to histopathologic differences (see below) and even though PMPs seem to be clonal proliferations with a potential for aggressive, local growth and recurrence, they are characterized by an excellent outcome and do not have the same malignant potential as IMT. These same scientists also group PSCNs with PMPs. (20,21)
This review will focus on what is currently known about these low-grade myofibroblastic proliferations (LGMPs) of the urinary bladder--which is the term we have chosen to embrace all of the above designations and entities.
A PubMed (US National Library of Medicine, Bethesda, Maryland) search was carried out to identify original articles focusing on this subject. We have based our review of the literature on selected study articles and textbooks, recently published review articles, editorials from peer-reviewed journals, and the reference list of each searched publication. All of these manuscripts were full-text, English-language, and published between 1980 and 2012. When necessary, we contacted by e-mail the corresponding authors of the article to obtain clarifications and/or details about the cases on which they had reported.
Because of the rarity of LGMPs affecting this anatomic site, we obtained most of the clinicopathologic features from an overall patient population composed of the most-relevant cases reported in the English-language literature (Table 1). (2-6,8,12,15,17-50) Because of the relative paucity of specific articles dealing with PMP and/or PSCN, fewer data were available regarding these entities, compared with those dealing with IMT. Information regarding tumor designation, patients' characteristics, primary symptoms, tumor size, urinary bladder infiltration, treatment, and follow-up was obtained from each selected publication. The LGMPs shown in the various figures are unpublished and are selected from files belonging to our Section of Pathology and the Department of Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Arcispedale Santa Maria Nuova (Reggio Emilia, Italy).
EPIDEMIOLOGY AND CLINICAL PRESENTATION
Among the LGMPs, IMT, which was first described in the lung, is the most-frequently reported entity. (51) In the genitourinary tract, the urinary bladder is the most common anatomic site of origin of this lesion; additional locations include the kidney, urethra, prostate, ureter, and rete testis. (52)
Our review of the most-salient literature concerning cases of LGMP occurring in the urinary bladder (Table 1) showed that most of those cases occur during the fourth and fifth decades of life, with men more frequently affected than women (1.33:1 ratio), and without any perceptible difference between IMT and PMP. Overall, this male predominance seems to be less evident when considering patients younger than 18 years. The case distribution during the various decades of life is shown graphically in Figure 1.
In LGMPs, painless hematuria was the most-common symptom, whereas dysuria, pelvic pain, and symptoms related to obstruction or infections occurred more rarely (Table 1). Unlike extragenitourinary tract IMT, systemic symptoms--such as fever and weight loss--are uncommon in urinary bladder locations. (53) In only one case were myalgia, fatigue, and fever reported; however, at least in part, these signs and symptoms could have been secondary to an underlying systemic lupus erythematosus. (48)
PATHOLOGIC AND IMMUNOHISTOCHEMICAL FINDINGS
Grossly, LGMPs of the urinary bladder may be either polypoid masses or, less frequently, rather flat nodules, with or without surface ulceration. On cut section, their color is gray-white to yellow with a macroscopic appearance from fascicular to myxoid. (7,20,52) In the cases reported (Table 1), at first diagnosis, the tumor's greatest diameter was between 1 and 11 cm (median, 4 cm), with no difference between patients aged older than or younger than 18 years, and no site predilection.
Three main histopathologic patterns of IMT have been described: (1) a myxoid/vascular pattern (Figure 2, A) characterized by spindle/stellate myofibroblasts with abundant eosinophilic cytoplasm and vesicular nuclei; (2) a compact, spindle cell proliferation (Figure 2, B)--sometimes with some ganglion-like cells--arranged in fascicular or storiform patterns, with varying degrees of cellularity; and (3) a hypocellular, fibrous pattern (Figure 2, C), displaying abundant collagen, plasma cells, lymphocytes, and eosinophils (similar to desmoid fibromatosis). (52)
These patterns are also typically characterized by varying amounts of acute (with neutrophils and/or eosinophils), chronic (lymphoplasmacellular), or mixed inflammatory infiltrates (Figure 2, D). Myofibroblasts show elongated-to-oval nuclei, often with prominent nuclei, and do not exhibit clear-cut atypia. The reported mitotic index ranges from 0 to 20 mitoses/10 high-power fields with most IMTs having a mitotic count of less than 5. (20) Based on Table 1, muscularis propria infiltration is common (about 60% of the whole patient population), whereas perivesical soft tissue invasion is not frequent (about 5% of the cases, without any apparent difference between IMT and PMP).
Necrosis is usually quite rare to absent in LGMPs of the urinary bladder (Figure 2, E). Iczkowski et al (5) found no necrosis in any of their cases and, in addition, suggested it as key to a diagnosis of sarcoma. Montgomery et al (6) detected necrosis in 30% of their patient population with IMT, whereas Harik et al (20) found it in 22 of 42 lesions (52%), even though it was mainly focal, minimal, and confined to the surface. Seven of those 22 cases (32%) showed necrosis (extensive in 2 of 7; 29%) in the deep urinary bladder wall and were associated with muscularis propria invasion. (20) Overall, when present, necrosis in LGMPs is rarely extensive and/or is located at the tumor-detrusor interface. Lesions with these findings should be carefully evaluated to rule out any malignancy.
Some authors (20,21,46,54) claim that, in the urinary bladder, IMT and PMP should be considered separate entities with sufficiently different clinical behavior to warrant their distinction on morphologic grounds. According to these scientists, the distinguishing histologic features of PMPs are haphazard-to-loose, fascicular arrangements of spindle cells, many of which have elongated, bipolar cytoplasmic processes that are often eosinophilic (rhabdomyoblast-like) (Figure 2, F); edematous-to-myxoid stroma with prominent vascularity and a variably dense, acute, and/or chronic inflammatory infiltrate; occasionally, focal, more-cellular fascicular areas, particularly in the deeper portions; rare occurrences of storiform and hypocellular, fibrous patterns; and inflammatory infiltrates that are generally less dense than they are in IMT. (54) The malignant potential of IMT of the genitourinary tract is seen in anecdotal cases of transformation into true inflammatory fibrosarcoma, which is characterized by increasing atypia and cellularity in a background superimposable on that of classic IMT (see index case in Figure 3, A through C). (6)
Moreover, the synchronous occurrence of a transitional-cell carcinoma, as either a separate nodule or admixed, has been reported sporadically (Table 1). (7) Interestingly, metastatic urothelial carcinoma may exhibit a similar myofibroblastic proliferation, whereas the corresponding primary tumor may not. (55)
In the LGMPs of the urinary bladder, there is significant immunohistochemical overlap between myofibroblastic proliferations diagnosed as IMT or PMP. In fact, they express vimentin (95%-100% of cases), smooth-muscle actin (48%-100%; Figure 4, A), AE1/3 (73%-78%; Figure 4, B), desmin (5%-80%; Figure 4, C), muscle-specific actin (62%), clone OSCAR keratin (70%), and CAM 5.2 (70%), whereas CK5/6 and 34PE12 seem not to be expressed. (1,6,10,52,54) Bladder IMT is more prone to express keratins than is IMT occurring in other genitourinary tract locations, and, rarely, findings are positive for myogenin or MyoD1. (52) Unlike bladder sarcomas, in IMT, p53 nuclear positivity is weak or even negative. (5)
Immunohistochemical analysis with an antianaplastic lymphoma kinase-1 (ALK-1) antibody is specific but only slightly sensitive for IMT (provided that myogenin and MyoD1 findings are negative because rhabdomyosarcoma may seldom express these markers). (1) Results for ALK-1 were found to be positive in 20% to 89% of urinary bladder IMTs (Figure 4D). (1,6,10,20,42,43,46)
The pathologic differential diagnosis of bladder LGMPs is summarized in Table 2.
IMAGING FINDINGS
Radiologic imaging plays a key role in the preoperative management and follow-up of patients with LGMP. Ultrasound, contrast-enhanced computed tomography, and magnetic resonance images provide valuable information on tumor size and infiltration of the urinary bladder wall. (56) On ultrasound, according to the particular case, LGMP can appear as either a well-defined, nonspecific mass or as simple bladder-wall thickening with variable echogenicity, and the lesion being described as hypoechoic or hyperechoic. On ecocolor Doppler (or ecopower Doppler), and especially on contrast-enhanced ultrasound examinations, LGMPs may appear as hypervascular nodules. (57-59) Computed tomography (Figure 5) may show either a focal or diffuse bladder-wall thickening and, more rarely, a polypoid mass; the lesion may be hypodense, isodense, or hyperdense and well enhanced after intravenous contrast medium administration. On magnetic resonance imaging, LGMP is characterized by low T1 signal intensity and nonhomogeneous high T2 signal intensity. In some cases, on T2 imaging, LGMP may show high signal intensity centrally, reflecting central necrosis, and low signal peripherally. Postcontrast, T1-weighted magnetic resonance imaging demonstrates heterogeneous enhancement with nonenhanced areas of necrosis. (59)
MOLECULAR GENETICS
Clonal genetic aberrations in the short arm of the chromosome 2 (region 21-23 of the long arm) have been described in approximately 50% to 60% of IMTs. This rearrangement involves the 2p23 region that contains the ALK gene, which encodes a tyrosine kinase receptor expressed predominantly in the central nervous system and is a member of the superfamily of insulin growth-factor receptors. (60) Although fluorescence in situ hybridization (FISH) in many IMTs has shown ALK gene rearrangement, in most cases, the fusion partner has not been identified. The ALK gene rearrangements identified that have led to fusion with other genes include ATIC, (41) CARS, (61,62) TPM3, (63-65) TPM4, (63,65,66) TPM3 and TPM4, (67) CLTC, (60,65,68) RANBP2, (60,69) and SEC31L1 (SEC31A). (70) The ALK-ATIC rearrangement has been reported in bladder IMTs. (41)
In normal ALK signaling, ligand-induced homodimerization of the extracellular domains brings the tyrosine kinase domains into sufficient proximity to enable transphosphorylation and kinase activity, whereas translocations resulting in pathogenic fusion partners provide dimerization domains that are ligand-independent, leading to unregulated constitutive kinase activity. (71)
Fluorescence in situ hybridization analysis can be used to detect ALK gene break-apart rearrangements in IMT (Figure 6). The FISH kits are a mixture that consists of 2 fluorophore-labeled DNA probes in hybridization buffer containing ALK-upstream and ALK-downstream probes characterized by 2 different colors. The hybridization targets of these 2 probes are situated on opposite sides flanking the breakpoint of the ALK gene. Nuclei with ALK gene rearrangement display the normal ALK region as a 2-color fusion signal, whereas, if a breakapart has occurred, the 2color signals split, separating them. (52) Using FISH analysis, rearrangements of the ALK gene have been detected in 67% to 72% of IMTs of the urinary bladder. (6,20,43,46) Some PMPs and PSCNs show positive immunohistochemistry for ALK and/or express ALK gene rearrangements. (20,52) Detection of ALK gene rearrangements by FISH is fundamental to distinguishing IMTs from other spindle cell proliferations of the urinary bladder, especially when the immunohistochemical analysis is not conclusive. (46)
PATHOGENESIS
Some studies on extragenitourinary tract IMT have investigated its etiology; however, its pathogenesis remains obscure. In addition, no studies have clarified the pathogenesis of genitourinary IMT. An underlying infection has long been thought to be the primum movens of this spindle cell proliferation. Various infectious agents have been detected in IMTs, such as bacteria (Bacteroides corrodens, Klebsiella pneumoniae, Mycobacterium avium, Corynebacterium jejuni, Bacillus sphaericus, Escherichia coli, and Coxiella burnettii) and viruses, the most-frequently reported being Epstein-Barr virus and human herpesvirus 8. (52,72,73)
An autoimmune etiology of IMT has been postulated based on single reports. In one case, an IMT of the submandibular gland was found in a patient with polyclonal hypergammaglobulinemia, high titers of antinuclear antibody, but without any signs of known autoimmune disease. (74) Additional reports described cases of IMT of the spleen with thrombocytopenic purpura and IMT with Riedel thyroiditis. (52)
In 20 LGMPs listed in Table 1, previous urinary bladder instrumentation was ascertained, so that they were labeled as PSCN.
TREATMENT
As shown in Table 1, 65% (185 of 285) of the reported cases were treated with transurethral resection (TUR), 27% (77 of 285) with partial cystectomy, 6% (16 of 285) with total cystectomy, and 3% (7 of 285) with other surgical procedures. In fact, surgical management is a sign of the controversy surrounding the nature of LGMPs, the consequent limited workload of such lesions for a single surgeon, and the anecdotal and subjective judgments. (6,12,20,45)
Based on available data from the literature, even though the malignant potential of LGMP of the genitourinary tract is still uncertain and is sometimes difficult to evaluate, the indolent and often benign clinical course that characterizes most of the cases does not warrant aggressive therapy (radical cystectomy, radiation, or chemotherapy). (52) On the other hand, follow-up cystoscopy and biopsies are mandatory to detect potential recurrences early on, especially in large, multinodular, and/or incompletely resected lesions. (75)
OUTCOME
The World Health Organization classification of soft tissue tumors classifies IMTs as neoplasms of intermediate malignancy, subtype rarely metastasizing. (76) According to this classification, extrapulmonary IMTs have a recurrence rate of approximately 25% (related to location, resectability, and multinodularity), whereas only a few cases (<5%) metastasize. (53) In most cases, it is difficult to predict the recurrence and/or malignant potential on the basis of histopathologic findings alone. (76)
In our review of the literature (Table 1), data on patients' follow-up were available in 218 cases. Only 7% (15 of 218) of patients with urinary bladder myofibroblastic proliferations experienced local recurrence: 5% (10 of 218) with IMT, or similar designations, and 2% (25 of 218) with myofibroblastic lesions clearly labeled as PMP. None of them developed metastases or died from the disease.
In 5 of 218 cases (2.3%) there was a synchronous carcinoma (4 urinary bladder transitional-cell carcinomas and 1 renal clear-cell carcinoma). Of 9 deaths, 1 patient (of 9; 11%) died from urosepsis, 1 (of 9; 11%) from postoperative infection, 3 (of 9; 33%) from unrelated causes, 1 (of 9; 11%) of inflammatory fibrosarcoma, 2 (of 9; 22%) from synchronous bladder transitional-cell carcinoma, 1 (of 9; 11%) from neurofibromatosis complications, and 1 (of 9; 11%) from unknown causes.
We need more data to explore ALK-1 as a prognostic factor in IMT and related myofibroblastic lesions of the urinary bladder.
UNSOLVED QUESTIONS
Although more than 30 years have passed since its first description, several questions remain unanswered regarding LGMP of the urinary bladder. The most urgent problem seems to be both the nomenclature and the real nature of these lesions.
Some authors feel that PMP and PSCN represent the same entity, which should be separated from true IMT. Grounds for this classification are a fairly distinct histopathologic picture and the quite different clinical behavior, with IMT representing proliferations with some malignant potential. (20,21,46,54) At the opposite end of that spectrum, the inflammatory fibrosarcoma shares a similar background with clearly malignant spindle cells and, above all, a much worse prognosis. (6) A widespread unifying theory hypothesizes that such lesions would be part of a single continuum, ranging from benign pseudosarcomatous lesions to low-grade sarcomas. (52) Molecular genetics does not yet help us to solve the arcana of these LGMPs. In fact, only a fraction of these cases (but a fraction that includes IMT, PMP, and PSCN cases) harbor ALK gene rearrangements with evidence of clonal proliferation, whereas the remaining LGMPs are either reactive or due to an unknown genetic abnormalities. (20,52) Unfortunately, so far, ALK expression and ALK gene rearrangements are unable to predict prognosis. In addition, in most cases, the histopathologic appearance alone does not help us forecast the clinical behavior of a given myofibroblastic proliferation of the urinary bladder.
CONCLUSIONS
The LGMPs of the urinary bladder include different lesions extending from benign, pseudosarcomatous entities to low-grade, inflammatory fibrosarcomas, and they mainly affect patients in their middle decades. With the exception of frank sarcomas, these lesions should be considered of uncertain clinical behavior, even though no metastatic cases in this anatomic location have been reported in the English-language literature. However, in view of the indolent clinical course, in most cases, aggressive treatments (such as radical cystectomy, chemotherapy, and radiotherapy) are probably unjustified. (52)
Further investigations dealing with the molecular genetics in LGMPs of the urinary bladder will certainly help us to clarify their nature and to establish more-sound classifications and prognostic criteria.
Caption: Figure 1. Number and distribution during the various decades of life of the urinary bladder low-grade myofibroblastic proliferation cases published in the English-language literature. This graph is based on manuscripts with sufficient information on the ages and genders of single patients. Black columns, males; gray columns, females.
Caption: Figure 2. Histopathology. A, The myxoid/vascular pattern shows spindled myofibroblasts, which usually lack clear nuclear hyperchromasia and pleomorphism. These elements seem to float in a markedly myxoid stroma containing some thin-walled blood vessels. B, Some cases are more compact and cellular. The myofibroblasts are arranged in medium-sized fascicles and placed in a stroma rich in collagen. C, Sometimes, these lesions are hypocellular with an abundant, fibrous stroma. D, There are different degrees of admixed, inflammatory cells, such as lymphocytes, plasma cells, and granulocytes. E, Occasionally, limited areas of tumor necrosis (asterisk) may be found throughout the spindle cell proliferation. F, Some lesions may be characterized by spindled and/or round, rhabdomyoblast-like myofibroblasts (hematoxylin-eosin, original magnifications X10 [A through C], X20 [D], X4 [E], and X40 [F]).
Caption: Figure 3. Malignant transformation. A 45-year-old woman with a twice-recurring inflammatory myofibroblastic tumor (IMT) of the urinary bladder, which, at follow-up, turned into a lethal inflammatory fibrosarcoma (unpublished index case). A, The original IMT was composed of a spindle cell proliferation in an extremely loose stroma. These elongated cells displayed myofibroblastic morphology without clear-cut atypia. B, The first recurrence (8 months later), with a more cellular pattern, where the neoplastic cells showed a hyperchromatic nucleus and some atypical mitotic figures. C, The second recurrence (6 months after first recurrence) consisted of a highly cellular proliferation, where the neoplastic elements are clearly atypical and pleomorphic (hematoxylin-eosin, original magnifications X40 [A through C]).
Caption: Figure 4. Immunohistochemistry. A, Immunohistochemical analysis showing marked and diffuse positivity for smooth muscle actin. B, Keratin AE1/ AE3 may be mildly and focally positive (arrowhead). C, Occasionally, desmin may display sparse positivity (arrow; the arrowhead shows muscularis propria infiltration). D, Intense positivity for ALK-1. Immunohistochemical reactions were revealed with 3,3'- diaminobenzidine and mildly counterstained with hematoxylin (original magnifications X20 [A through D]).
Caption: Figure 5. Contrast-enhanced tomography. Triphasic, contrast-enhanced, axial, multidetector computed tomography of the pelvis (arterial phase) showing an irregular thickening of the right-hand side of the urinary bladder wall (arrow), which also involves the homolateral ureter outlet.
Caption: Figure 6. Fluorescence in situ hybridization (FISH) for the anaplastic lymphoma kinase (ALK)-1 gene. This analysis has been carried out using dual-color, breakapart probes. Rearrangement of the above gene is confirmed by the presence of cells with separate red and green signal (arrows), whereas some myofibroblasts show normal fusion signal (arrowheads) (image courtesy of William R. Sukov, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota). The FISH analysis of a bladder inflammatory myofibroblastic tumor is achieved with a breakapart strategy that uses probes flanking both telomeric and centromeric sides of the ALK locus (original magnification X100).
We are indebted to Gabriella Becchi, B. Tech, for her competent technical assistance. In addition, we would like to express our gratitude to the various authors who provided additional information on their published cases. Lastly, a special thank to William R. Sukov, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, for providing Figure 6; to Alberto Cavazza, MD, Department of Pathology, IRCCS, Arcispe dale Santa Maria Nuova, Reggio Emilia, Italy, for his precious help in retrieving adequate histologic material and to Augusto Vaglio, MD, PhD, Department of Nephrology, University Hospital, Parma, Italy, for his critical review of this manuscript.
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(76.) Coffin C, Fletcher J. Inflammatory myofibroblastic tumour. In: Fletcher C, Unni KK, Mertens F, eds. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2002:91-93. World Health Organization Classification of Tumours; vol 4.
Sara Alquati, MD; Federica Alessandra Gira, MD; Veronica Bartoli, MD; Sandro Contini, MD; Domenico Corradi, MD
Accepted for publication September 27, 2012.
From the Department of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; the Department of Surgical Sciences, Section of Radiology, University of Parma, Parma, Italy (Dr Gira); the Department of Clinical and Experimental Medicine, Section of Occupational Medicine, University of Parma (Dr Bartoli); the Department of Surgical Sciences, University of Parma (Dr Contini); and the Department of Biomedical, Biotechnological, and Translational Sciences, Section of Pathology, University of Parma (Dr Corradi).
The authors have no relevant financial interest in the products or companies described in this article.
Reprints: Domenico Corradi, MD, Department of Biomedical, Biotechnological, and Translational Sciences, Section of Pathology, University of Parma Via Gramsci 14, 43126 Parma, Italy (e-mail: domenico.corradi@unipr.it).
Table 1. Review of the Literature Regarding Cases of Low-Grade
Myofibroblastic Proliferations Occurring in the Urinary Bladder
Designation,
No. of Cases
(% of all Cases), Sex,
Source, y N = 287 (a) Age, (b) y M/F
Roth, (2) 1939 IP, 1 (0.4) 32 0/1
Proppe et al, IP, 1 (0.4) 29 1/0
(3) 1984
Olsen, (22) 1984 IP, 1 (0.4) 24 0/1
Nochomovitz et IP, 2 (0.7) 22; 73 1/1
al, (8) 1985
Ro et al, (23) 1986 PFT, 2 (0.7) 52; 56 0/2
Young et al, IP, 1 (0.4) 59 1/0
(24) 1987
Wick et al, IP, 2 (0.7) 55; 60 2/0
(25) 1988
Stark et al, IP, 2 (0.7) 19; 16 1/1
(26) 1989
Albores-Saavedra PMP, 10 (3.5) 7 (2-16) 2/8
et al, (19) 1990
Huang et al, PSC, 1 (0.4) 45 1/0
(4) 1990
Hughes et al, PL, 4 (1.4) 48 (41-56) 1/3
(27) 1991
Dietrick et IP, 2 (0.7) 18; 37 1/1
al, (28) 1992
Lamovec et al, IP, 1 (0.4) 2 0/1
(29) 1992
N'Dow et al, IP, 1 (0.4) 18 0/1
(30) 1993
Ro et al, (17) 1993 PFT, 8 (2.8) 56 (40-58) 3/5
Jones et al, IP, 13 (4.5) 33 (19-60) 5/8
(15) 1993
Lundgren et al, (18) PSC, 12 (4.2) 50 (14-80) 4/8
Angulo et al, PMP, 2 (0.7) 16; 49 1/1
(31) 1994
Koirala et al, IP, 1 (0.4) 47 1/0
(32) 1994
Weidner, (33) 1995 IP, 1 (0.4) 61 1/0
Hojo et al, PMT, 11 (3.8) 8 (3-19) 7/4
(12) 1995
Horn et al, IP, 3 (1.0) 39 (35-49) 0/3
(34) 1997
Netto et al, IP, 5 (1.7) 7 (2-12) 3/2
(35) 1999
Gardner et al, IMT, 1 (0.4) 3 1/1
(36) 1999
Asanuma et al, IP, 1 (0.4) 7d 1/0
(37) 2000
Iczkowski et IP, 17 (5.9); 44 (15-83) 15/6
al, (5) 2001 PSC, 4 (1.4)
Schneider et IP, 2 (0.7) 3; 14 2/0
al, (38) 2001
Watanabe et PMT, 3 (1.0) 38 (10-47) 2/1
al, (39) 2001
Gyftopoulos et PSC, 1 (0.4) 24 1/0
al, (40) 2002
Debiec-Rychter et IMT, 1 (0.4) 46 1/0
al, (41) 2003
Tsuzuki et IMT, 14 (4.9) 41 (18-76) 9/5
al, (42) 2004 (d)
Freeman et IMT, 9 (3.1) 36 (13-51) 5/4
al, (43) 2004
Mergan et IMT, 3 (1.0) 7 (6-15) 1/2
al, (44) 2005
Montgomery et IMT, 39 (13.6) 46 (3-86) 26/13
al, (6) 2006 (d)
Hirsch et PMP, 21 (7.3) 39 (18-76) 6/15
al, (21) 2006
Harik et PMP, 42 (14.6) avg 47 (7-77) 32/10
al, (20) 2006
Houben et IMT, 1 (0.4) 10 0/1
al, (45) 2007
Sukov et IMT, 21 (7.3) 42 (26-88) 8/13
al, (46) 2007
Spiess et PFT, 7 (2.4); 62 (37-85) 6/11
al, (47) 2007 PSC, 10 (3.5)
Hoene et al, IMT, 1 (0.4) 27 0/1
(48) 2008
Lekas et PL, 1 (0.4) 36 0/1
al, (49) 2008
Lecuona et IMT, 1 (0.4) 3 1/0
al, (50) 2012
Major
Dimension, (b)
Source, y Symptoms cm
Roth, (2) 1939 Cystitis, hematuria 1.5
Proppe et al, NA NA
(3) 1984
Olsen, (22) 1984 Cystitis 1
Nochomovitz et Hematuria 5; 5
al, (8) 1985
Ro et al, (23) 1986 Hematuria 2; 4
Young et al, Hematuria 2
(24) 1987
Wick et al, Hematuria 3; 3
(25) 1988
Stark et al, Hematuria 3; 3
(26) 1989
Albores-Saavedra Hematuria, 3 (2-5)
et al, (19) 1990 strangury, dysuria
Huang et al, NA NA
(4) 1990
Hughes et al, Hematuria cystitis NA
(27) 1991
Dietrick et Hematuria, dysuria 8; 4
al, (28) 1992
Lamovec et al, Dysuria 3.5
(29) 1992
N'Dow et al, Hematuria 2
(30) 1993
Ro et al, (17) 1993 Hematuria 4 (2-8)
Jones et al, Hematuria, 5 (2-7)
(15) 1993 recurrent cystitis
Lundgren et al, (18) Hematuria, 3 (1.5-6)
cystitis, dysuria
Angulo et al, Hematuria, pain, 3.5; 4.5
(31) 1994 dysuria
Koirala et al, Hematuria 4
(32) 1994
Weidner, (33) 1995 Hematuria 2
Hojo et al, Hematuria, dysuria 5 (3-9)
(12) 1995
Horn et al, Pain, hematuria 2 (1.5-3)
(34) 1997
Netto et al, Suprapubic pain, 4.5; 2 (size
(35) 1999 hematuria, available in
irritative 2 cases)
voiding symptoms
Gardner et al, Dysuria, abdominal 4.7
(36) 1999 pain, increased
urinary frequency
Asanuma et al, Hematuria 1.5
(37) 2000
Iczkowski et Hematuria, urinary 3.2 (1.3-13)
al, (5) 2001 obstruction,
irritation
Schneider et Hematuria 4.3; 6
al, (38) 2001
Watanabe et NA 3 (2.5-4)
al, (39) 2001
Gyftopoulos et Increased urinary 11
al, (40) 2002 frequency
Debiec-Rychter et Hematuria 4
al, (41) 2003
Tsuzuki et NA NA
al, (42) 2004 (d)
Freeman et NA 5 (2-7.5)
al, (43) 2004
Mergan et Hematuria NA
al, (44) 2005
Montgomery et Hematuria avg 4.2
al, (6) 2006 (d) (1.2-12)
Hirsch et Hematuria, dysuria, 4 (0.6-12)
al, (21) 2006 abdominal pain
Harik et Hematuria, pelvic avg (1-10)
al, (20) 2006 pain, obstructive
symptoms
Houben et Dysuria, voiding 5.5
al, (45) 2007 symptoms
Sukov et NA NA
al, (46) 2007
Spiess et Hematuria, dysuria NA
al, (47) 2007
Hoene et al, Myalgias, fatigue, 6.5
(48) 2008 fever
Lekas et Hematuria, 2.4
al, (49) 2008 abdominal pain
Lecuona et Hematuria 8.2
al, (50) 2012
Bladder Treatment, (c)
Infiltration No. (%),
Source, y (No.) n = 285
Roth, (2) 1939 Muscularis propria PC, 1 (0.4)
Proppe et al, NA TUR, 1 (0.4)
(3) 1984
Olsen, (22) 1984 NA TUR, 1 (0.4)
Nochomovitz et NA PC, 1 (0.4);
al, (8) 1985 TUR, 1 (0.4)
Ro et al, (23) 1986 NA TUR, 1 (0.4);
PC, 1 (0.4)
Young et al, NA TUR, 1 (0.4)
(24) 1987
Wick et al, NA NA, 1 (0.4)
(25) 1988
Stark et al, Muscularis PC, 2 (0.7)
(26) 1989 propria (2)
Albores-Saavedra Muscularis propria PE, 1 (0.4);PC, 2
et al, (19) 1990 (6); perivesical (0.07); TUR, 6
fat (2);NA (2) (2.1); CYS,
1 (0.4)
Huang et al, NA CYS, 1 (0.4)
(4) 1990
Hughes et al, Muscularis TUR, 3 (1.1);
(27) 1991 propria (4) CYS, 1 (0.4)
Dietrick et Muscularis CYS, 1 (0.4);
al, (28) 1992 propria (2) TUR, 1 (0.4)
Lamovec et al, Perivesical and CYS, 1 (0.4)
(29) 1992 periurethral
tissue
N'Dow et al, Muscularis propria PC, 1 (0.4)
(30) 1993
Ro et al, (17) 1993 Muscularis propria TUR, 6 (2.1);
(3); lamina CYS, 2 (0.7)
propria (5)
Jones et al, Muscularis propria TUR, 8 (2.8);
(15) 1993 (10); perivisceral PC, 5 (1.8)
fat (2); lamina
propria (1)
Lundgren et al, (18) NA TUR, 11 (3.9);
TAR, 1 (0.4)
Angulo et al, NA PC, 2 (0.7)
(31) 1994
Koirala et al, Muscularis propria TUR, 1 (0.4)
(32) 1994
Weidner, (33) 1995 Muscularis propria PC, 1 (0.4)
Hojo et al, NA PC, 3 (1.1); TUR,
(12) 1995 2 (0.7); TUR-PC,
6 (2.1)
Horn et al, Muscularis propria PC, 2 (0.7);
(34) 1997 (1); lamina TUR, 1 (0.4)
propria (2)
Netto et al, NA TUR, 5 (1.8)
(35) 1999
Gardner et al, Fibroadipose tissue PC, 1 (0.4)
(36) 1999
Asanuma et al, Muscularis propria OE, 1 (0.4)
(37) 2000
Iczkowski et Lamina propria (3); TUR, 13 (4.6);
al, (5) 2001 muscularis propria PC, 8 (2.8)
(15); NA (3)
Schneider et Muscularis PC, 2 (0.7)
al, (38) 2001 propria (2)
Watanabe et NA PC, 3 (1.1)
al, (39) 2001
Gyftopoulos et Muscularis propria SEA, 1 (0.4)
al, (40) 2002
Debiec-Rychter et Muscularis propria CYS, 1 (0.4)
al, (41) 2003
Tsuzuki et Muscularis TUR, 14 (4.9)
al, (42) 2004 (d) propria (2)
Freeman et NA CYS, 3 (1.1); PC,
al, (43) 2004 5 (1.8);
TUR, 1 (0.4)
Mergan et NA PC, 3 (1.1)
al, (44) 2005
Montgomery et Muscularis PC, 7 (2.5);
al, (6) 2006 (d) propria (16) CYS, 1 (0.4);
TUR, 38 (13.3)
Hirsch et Muscularis propria TUR, 3 (1.1); PC,
al, (21) 2006 (13); muscularis 9 (3.2);
mucosae (4) NA, 1 (0.4)
Harik et Muscularis propria TUR, 30 (10.5);
al, (20) 2006 (28 of 32; 88%); CYS, 3 (1.1);
muscularis mucosae PC, 9 (3.2)
(32 of 38; 84%);
perivisceral fat
(3 of 8; 38%)
Houben et Perivesicular soft PC, 1 (0.4)
al, (45) 2007 tissues
Sukov et NA PC, 2 (0.7); TUR,
al, (46) 2007 19 (6.7)
Spiess et Muscularis propria TUR, 17 (6.0)
al, (47) 2007 (7); NA (10)
Hoene et al, Muscularis propria CYS, 1 (0.4)
(48) 2008
Lekas et NA TUR, 1 (0.4)
al, (49) 2008
Lecuona et Perivisceral fat SEA, 1 (0.4)
al, (50) 2012
Follow-up (b)
Source, y (mo) Additional Data
Roth, (2) 1939 NED (12)
Proppe et al, Re-excision of a Preexisting TCC-UB;
(3) 1984 recurrence after can be labeled PSCN
6 wk; NED (36)
Olsen, (22) 1984 NED (36)
Nochomovitz et NED (36; 3) 73-y-old patient
al, (8) 1985 died of unrelated
causes with no
evidence of disease
Ro et al, (23) 1986 NED (12;24)
Young et al, NED (42) 15 mo after surgery,
(24) 1987 in situ TCC-UB;
can be labeled PSCN
Wick et al, NA 55-y-old patient had
(25) 1988 previous surgery
for TCC-UB;
60-y-old patient
had previous TUR;
both labeled PSCN
Stark et al, NED (24;17)
(26) 1989
Albores-Saavedra Follow-up data
et al, (19) 1990 available for 8
pts; NED (24;
18-72)
Huang et al, NED (48)
(4) 1990
Hughes et al, NED (60; 48-108) Synchronous, invasive
(27) 1991 TCC-UB in 1 case
Dietrick et NED (12; 18)
al, (28) 1992
Lamovec et al, NED (8)
(29) 1992
N'Dow et al, NED (9)
(30) 1993
Ro et al, (17) 1993 NED (51;24-108)
Jones et al, NED (24; 6-64) 1 patient had surgery
(15) 1993 for TCC-UB at 15
mo; 1 case labeled
PSCN
Lundgren et al, (18) NED (60;1-180) 1 patient died from
postoperative
infection; 1 died
of unknown cause;
synchronous TCC-UB
in 2 cases; 1 case
labeled PSCN
Angulo et al, NED (144;228)
(31) 1994
Koirala et al, NED (10)
(32) 1994
Weidner, (33) 1995 NED (12) Synchronous renal
Hojo et al, NED (15;2 wk-42) cell carcinoma
(12) 1995
Horn et al, NED (18; 12-23) 2 cases labeled PSCN
(34) 1997
Netto et al, NED (18, 18, 42);2 NA
(35) 1999
Gardner et al, NED (3)
(36) 1999
Asanuma et al, NED (12)
(37) 2000
Iczkowski et Follow-up data 1 patient died of
al, (5) 2001 available for 20; urosepsis;
residual tumor in synchronous
2; NED (24; 5-132) low-grade TCC-UB
in 1 case; TCC in
situ at 1 y in 1
case; 4 cases
labeled PSCN
Schneider et NED (NA)
al, (38) 2001
Watanabe et NED (96; 72-156)
al, (39) 2001
Gyftopoulos et NED (12)
al, (40) 2002
Debiec-Rychter et NA AL[K.sup.+] with
al, (41) 2003 both IHC and FISH.
Tsuzuki et NA Generic local
al, (42) 2004 (d) recurrence in 2
cases; ALK in 10
cases with IHC
Freeman et NED (16;5-48); ALK: IH[C.sup.+] in
al, (43) 2004 follow-up data 8 cases,
available for 6 pts [FISH.sup.+] in 4
(out of 6; 67%).
Mergan et NED (24; 2-60) AL[K.sup.+] with IHC
al, (44) 2005
Montgomery et Follow-up data ALK: IH[C.sup.+] in
al, (6) 2006 (d) available for 32; 18, [FISH.sup.+]
recurrence in 9, in 12;8 cases
with 2 recurrences labeled PSCN
in 2 cases; 2
lethal, synchronous
sarcomatoid TCC; 1
lethal case
diagnosed as
inflammatory
fibrosarcoma; NED
in remaining cases
(24; 3-120)
Hirsch et Recurrence in 2 cases ALK: IH[C.sup.+] in
al, (21) 2006 with 2 recurrences 10 (of 19; 53%),
in 1; NED FISH-in the 6
(27;3-108) cases evaluated;
4 cases labeled
PSCN
Harik et Follow-up data ALK: IH[C.sup.+] in
al, (20) 2006 available for 28 12, [FISH.sup.+]
pts; recurrence in in 4 (of 6 cases;
3 cases; 3 alive 67%); 9 labeled
with disease; PSCN; 1 patient
NED (24) with
neurofibromatosis
died of its
complicacy
Houben et NED (6) AL[K.sup.+] with IHC
al, (45) 2007
Sukov et NED (34; 7-70) ALK: IH[C.sup.+] in
al, (46) 2007 13; [FISH.sup.+]
in 14
Spiess et NED (36; 2-157) 2 pts died from other
al, (47) 2007 diseases
Hoene et al, NED (6) Systemic lupus
(48) 2008 erythematosus;
AL[K.sup.+] with
IHC, [FISH.sup.-]
Lekas et NED (36) AL[K.sup.+] with IHC
al, (49) 2008
Lecuona et NED (7) AL[K.sup.+] with IHC
al, (50) 2012
Abbreviations: ALK, anaplastic lymphoma kinase; avg, average;
CYS, cystectomy; FISH, fluorescence in situ hybridization; IHC,
immunohisto-chemistry; IMT, inflammatory myofibroblastic tumors;
IP, inflammatory pseudotumor; NA, not available; NED, no evidence
of disease; OE, open excision; PC, partial cystectomy; PE, pelvic
exenteration; PFT, pseudosarcomatous fibromyxoid tumor;
PL, pseudosarcomatous lesion; PMP, pseudosarcomatous
myofibroblastic proliferations; PMT, pseudosarcomatous
myofibroblastic tumor; PSCN, pseudomalignant spindle cell nodule;
pts, patients; SEA, suprapubic extraperitoneal approach; TAR,
transabdominal resection; TCC, transitional-cell carcinoma; TUR,
trans-urethral resection; UB, urinary bladder.
(a) Cases by designation, No. (%), n = 287: IMT, 91 (31.7);
IP, 57 (19.9); PFT, 17 (5.9);PL, 5 (1.7); PMP, 75 (26.1); PMT,
14 (4.9); PSC, 28 (9.8).
(b) When multiple cases are reported, data are expressed as
median value with its range.
(c) Cases by treatment, No. (%), n = 285: CYS, 16 (5.6); NA, 2 (0.7);
OE, 1 (0.4); PC + TUR-PC, 77 (27.0); PE, 1 (0.4); SEA, 2 (0.7);
TAR, 1 (0.4); TUR, 185 (64.9).
(d) These data may be slightly different than those in the
original article because they were directly obtained after
contacting the corresponding authors.
Table 2. Differential Diagnosis
IMT (a) PMP/PSCN (a) LM
Cell atypia Absent or Absent or Absent or
minimal minimal minimal
Mitoses Few Few Absent or rare
Necrosis Absent or Absent Absent
superficial
(minimal if
present)
Stroma Myxoid or Mainly Scarce
fibrous myxoid
Inflammation Present Present Absent
Muscularis Frequent Frequent In the
propria muscularis
infiltration propria
ALK-1 [+ or -] [+ or -] -
CD34 - - [+ or -]
c-Kit (CD117) - - -
Cytokeratin [+ or -] [+ or -] -
Desmin [+ or -] [+ or -] +
DOG-1 - - -
EMA - - Rare
h-Caldesmon - - +
Muscle-specific [+ or -] [+ or -] +
actin
MyoD1 Rare - -
Myogenin Rare - -
p63 - -
SMA [+ or -] [+ or -] +
S100 - -
Vimentin + + +
LG-LMS SC LG-IFS
Cell atypia Minimal or Moderate or Minimal or
moderate severe moderate
Mitoses Frequent Frequent to Frequent
diffuse
Necrosis Focal Frequent Focal or
zonal
Stroma Scarce Scarce Myxoid or
fibrous
Inflammation Absent Absent or Present
minimal
Muscularis In the muscularis Frequent Frequent
propria propria often
infiltration with whole
wall infiltration
ALK-1 - - [+ or -]
CD34 [+ or -] -
c-Kit (CD117) - -
Cytokeratin Rare + [+ or -]
Desmin + [+ or -] [+ or -]
DOG-1
EMA - + -
h-Caldesmon + -
Muscle-specific [+ or -] [+ or -]
actin
MyoD1
Myogenin - -
p63 [+ or -] -
SMA + [+ or -] [+ or -]
S100 - -
Vimentin + [+ or -] +
EGIST
Cell atypia Minimal to
severe
Mitoses Rare to
frequent
Necrosis Absent to
diffuse
Stroma Scarce to
fibrous
Inflammation Absent
Muscularis Frequent
propria
infiltration
ALK-1 -
CD34 [+ or -]
c-Kit (CD117) +
Cytokeratin -
Desmin Rare
DOG-1 +
EMA Rare
h-Caldesmon [+ or -]
Muscle-specific [+ or -]
actin
MyoD1
Myogenin
p63
SMA [+ or -]
S100 [+ or -]
Vimentin +
Abbreviations: ALK-1, anaplastic lymphoma kinase-1; EMA, epithelial
membrane antigen; IMT, inflammatory myofibroblastic tumor; EGIST,
extragastrointestinal gastrointestinal stromal tumor; LG-IFS,
low-grade inflammatory fibrosarcoma; LG-LMS, low-grade
leiomyosarcoma; LM, leiomyoma; PMP, pseudosarcomatous myofibroblastic
proliferation; PSCN, postoperative spindle cell nodules; SC,
sarcomatoid carcinoma; SMA, smooth muscle actin.
(a) See text "Pathologic and Immunohistochemical Findings" section
for detailed treatment.
----------
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| Author: | Alquati, Sara; Gira, Federica Alessandra; Bartoli, Veronica; Contini, Sandro; Corradi, Domenico |
|---|---|
| Publication: | Archives of Pathology & Laboratory Medicine |
| Article Type: | Report |
| Geographic Code: | 1USA |
| Date: | Aug 1, 2013 |
| Words: | 8545 |
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