Histologic typing of bladder cancer
In 2003, the most recent World Health Organization (WHO) "Blue Book" on Pathology and Genetics of Tumours of the Genitourinary System was published [1]. Given in Table 1 is the WHO 2003 classification of tumours of the urinary bladder:

Table 1. WHO 2003 histological classification of tumors of the urinary bladder

Urothelial tumours Infiltrating urothelial carcinoma with squamous differentiation with glandular differentiation with squamous and glandular differentiation Nested variant Microcystic variant Micropapillary variant Lymphoepithelioma-like carcinoma Lymphoma-like variant Plasmacytoid variant Sarcomatoid (w./w.o heterologous elements) Giant cell variant Undifferentiated carcinoma Other variants Non-invasive urothelial neoplasias Hyperplasia (flat and papillary) Dysplasia (include normal urothelium and atypia) Urothelial papilloma Urothelial papilloma, inverted type Non-invasive papillary urothelial neoplasm of LMP Non-invasive papillary urothelial carcinoma (low grade) Non-invasive papillary urothelial carcinoma (high grade) Squamous neoplasms Squamous cell carcinoma Verrucous squamous cell carcinoma Squamous cell papilloma Glandular neoplasms Adenocarcinoma Urachal carcinoma Clear cell adenocarcinoma In situ adenocarcinoma Villous adenoma Neuroendocrine tumours Small cell carcinoma Paraganglioma Carcinoid Mesenchymal and miscellaneous tumours Rhabdomyosarcoma Leiomyosarcoma Angiosarcoma Osteosarcoma Malignant fibrous histiocytoma Leiomyoma Granular cell tumour Neurofibroma Haemangioma Malignant melanoma Lymphoma Metastatic tumours and secondary extension

This classification system provides a modern, evidence-based, foundation for clinical management of patients with these conditions and is recommended for routine use. A comparison of the WHO 2003 system with the WHO 1999 scheme [2] reveals several changes.

First, in WHO 2003 the term urothelial is used exclusively to refer to tumors derived from the epithelial lining of the bladder rather than the WHO 1999 use of urothelial or transitional cell. This is warranted since this lining, the urothelium, is unique and does not represent any sort of transition from one cell type to another [3, 4] .

Urothelial Carcinoma Variants: Diagnostic Terminology
In the WHO 2003 classification, these are subtle alterations in the diagnostic terminology of variants of urothelial carcinoma. Urothelial carcinoma with malignant squamous and/or glandular epithelium is urothelial carcinoma with squamous and/or glandular differentiation (WHO 2003) rather than metaplasia (WHO 1999). Squamous differentiation overall occurs in 21% of urothelial carcinomas, with increasing frequency with increasing grade and stage [1, 5] . The proportion of the squamous component varies considerably; only if the tumor is comprised of pure malignant squamous cells should squamous cell carcinoma be diagnosed. Similarly, only pure glandular carcinomas should be denoted as adenocarcinoma of the urinary bladder. Urothelial carcinoma with glandular differentiation is less common, at 6% of all urothelial carcinomas, than those with squamous differentiation [1, 5] . Glandular differentiation here is reserved for the formation of true luminal spaces, and not intracytoplasmic mucin. A visual inspection estimate of percentage squamous and/or glandular differentiation should be given. Squamous differentiation may be associated with a poor response to surgery, radiation, and chemotherapy, while the clinical significance of glandular areas is uncertain.

Carcinosarcoma and spindle cell carcinoma (WHO 1999) are now sarcomatoid carcinoma, with or without heterologous elements (WHO 2003). Urothelial carcinoma with ectopic placental glycoprotein production (WHO 1999) is now urothelial carcinoma with trophoblastic differentiation. Newly-recognized variants in the WHO 2003 publication include urothelial carcinoma with giant cells and a lymphoma-like variant of urothelial carcinoma [1]. Both are distinctly uncommon. Urothelial carcinoma with giant cells should be distinguished from urothelial carcinoma with foreign-body or osteoclast-like giant cells in the stroma [6, 7] and urothelial carcinoma with trophoblastic differentiation [6], where the giant cells are syncytiotrophoblasts. Lymphoma-like and the plasmacytoid variants of urothelial carcinoma can represent a significant diagnostic pitfall, especially in small biopsy tissue samples. Immunostains for pan-cytokeratin, CK7, and (sometimes) CK20 should be positive, with negative lymphoid markers.

A urothelial carcinoma variant included in the WHO 1999 book but not the WHO 2003 text is the osteoclastic variant [6]. The WHO 2003 approach does not separate stromal responses as variants, but it is important to be aware that unusual stromal responses include the aforementioned osteoclast giant cells, pseudosarcomatous stroma, a prominent lymphoid infiltrate, and stromal osseous metaplasia [6].

Deceptively Benign - Appearing Variants of Urothelial Carcinoma

Inverted pattern Small tubular pattern Microcystic pattern Nested pattern

The WHO 2003 classification does not formally include inverted or small tubular patterns as variants, but does list and describe the microcystic and nested variants.

Whereas most papillary urothelial carcinomas exhibit an exophytic architectural arrangement of finger-like papillae, endophytic urothelial neoplasms display either a broad front verrucous carcinoma-like growth or inverted papilloma-like growth. Diagnostic challenges arise due to difficulty in the differential diagnosis with benign inverted papilloma and in assessment of invasion [1, 8, 9] . Features useful for diagnosis of urothelial carcinomas with inverted papilloma-like growth include cords and trabeculae with irregularity of width and with transition into solid areas, minimal to absent maturation, spindling or palisading, and cytologic atypia [7, 8] .

Small tubular pattern urothelial carcinoma could be mistaken for nephrogenic adenoma [9, 10] . It is briefly mentioned within the nested variant section in the 2003 WHO book, where it is noted that some urothelial carcinoma nests have small tubular lumens [1, 8, 11] . It is potentially confounding that the nuclear atypia of the tubular lining cells is minimal. Here, the diagnosis of carcinoma is rendered upon recognition of the haphazard disposition of the tubules, variation of tubular shape, and frequent muscle wall invasion [8]. The clinical significance of this pattern is not clear, since these are so few cases, and many are admixed with a nested pattern, which imparts a worse prognosis.

Microcystic urothelial carcinoma demonstrates variable-sized cysts ranging up to 1 to 2 mm in diameter [1, 8, 12, 13, 14] . The cysts are round to oval and may contain necrotic material or pink secretions [1]. The lining cells layer may be flattened or denuded [12]. The differential diagnosis includes cystitis cystica, cystitis glandularis, and nephrogenic adenoma [1]. The correct diagnosis is achieved by detection of association with usual urothelial carcinoma [12], haphazard and infiltrative growth, and cyst size and shape variability [8].

The nested variant of urothelial carcinoma is a rare, aggressive neoplasm with an appearance that can simulate von Brunn nests, cystitis cystica and glandularis, inverted papilloma, and nephrogenic adenoma [1, 8, 14, 15, 16, 17, 18] . Clues that are of aid in establishing the diagnosis are the high-density, nearly confluent nests that can anastomose and invade muscularis propria (wall). Nuclear atypia may be only focally present, and is often found in the deeper aspects of the proliferation. Although the nested variant of urothelial carcinoma has a higher proliferation index than florid von Brunn nests by MIB-1 immunostaining (8.8% vs. 2.8%), and a higher p53 immunopositivity (4.2% vs. 1.5%), the degree of overlap precludes use of these markers as diagnostic tools [19].

Typing of Poorly-differentiated/undifferentiated Urothelial Carcinoma:
Immunohistochemical Markers
Substantiation of urothelial differentiation in the differential diagnosis with other neoplasms can be accomplished by an immunophenotypic marker panel:

Marker	Positivity in Urothelial Carcinoma [20]
High molecular weight cytokeratin (antibody 34bE12)	65%
p63	85%
CK7	83-100%
CK20	15-74%
Thrombomodulin	69-91%
Uroplakin III	57%

Note that of these markers, only uroplakin III is specific for urothelial differentiation (21).

Grading of Non-invasive Urothelial Tumors
Histological grading is of prime importance for non-invasive urothelial tumors, is of probable importance in pT1 tumors, and is of questionable significance in pT2 and higher stage tumors since these are mainly high-grade [1]. The diagnostic classification and grading of papillary urothelial neoplasms has been controversial [22, 23, 24, 25] .

The WHO 2003 recommended nomenclature for non-invasive urothelial tumors [1] is identical to the WHO-ISUP 1998 classification [3]. The chief difference compared to the WHO 1999 scheme is that rather than three grades of papillary urothelial carcinoma, there are two - low grade and high-grade - in the WHO 2003 classification (Table 1). However, it is specifically stated in the text that for the high-grade tumors pathologists have the option of recording the presence or absence of diffuse anaplasia in a comment. This seems to leave open the possibility that high-grade carcinomas should be divided into two grades. Arguments against this [8] include the finding that only a small percentage (4 to 5%) of high-grade non-invasive papillary cancers harbor marked anaplasia [26, 27] and the potential confusion that may arise when using the G1 to G3 systems of WHO 1973 and WHO 1999, which differ in definitions. The two-tiered WHO 2003 grading of carcinoma was deemed a "work in progress" [1]. The authors of the WHO 2003 system cite genetic studies that suggest there are "two major subtypes of urothelial neoplasms which might have a distinctly different clinical course" - genetically stable tumors which include most non-invasive low-grade carcinomas and genetically unstable non-invasive high-grade carcinomas and invasive carcinomas [1]. Currently, these genetic differences and specific molecular markers, such as cytokeratin 20, p53, p63, CD44, FGFR3, and Ki-67 [1, 28] hold promise for the future, but are not in routine use in grading of urothelial proliferations. Prospective evaluation of the WHO 2003 grading system and of molecular aids in grading are desirable goals for the future.

Staging of Urothelial Carcinoma
Currently, pathologic staging of bladder cancer should be performed according to the 2002 AJCC/UICC TNM staging guidelines [29]

Table 2. 2002 AJCC/UICC TNM Staging of Bladder Carcinoma

Primary Tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Ta Non-invasive papillary carcinoma Tis Carcinoma in situ : "flat tumor" T1 Tumor invades subepithelial connective tissue T2 Tumor invades muscle pT2a Tumor invades superficial muscle (inner half) pT2b Tumor invades deep muscle (outer half) T3 Tumor invades perivesical tissue pT3a microscopically pT3b macroscopically (extravesical mass) T4 Tumor invades any of the following : prostate, uterus, vagina, pelvic wall, abdominal wall T4a Tumor invades prostate, uterus, vagina T4b Tumor invades pelvic wall, abdominal wall Regional Lymph Nodes (N) Regional lymph nodes are those within the true pelvis; all others are distant lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single lymph node, 2 cm or less in greatest dimension N2 Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension N3 Metastasis in a lymph node, greater than 5 cm in greatest dimension Distant Metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

From reference [29]. See that reference for stage groupings.

This staging method does not differ from the 1997 TNM system. Accurate pathologic staging of bladder cancer remains a critical task that allows for appropriate prognostic and therapeutic stratification of patients. Recognition of invasion and anatomic depth of invasion by carcinoma is vital. Most invasive bladder cases are high-grade [1, 8] although a minority of pT1 cancers are low-grade [8], especially the deceptively-benign variants discussed above. Diagnostic patterns of lamina propria invasion as recently presented [8] can facilitate pT1 stage assignment:

Table 3. Histologic Patterns of Lamina Propria Invasion

Invading epithelium:	irregularly shaped nests single-cell infiltration irregular or absent basement membrane tentacular finger-like processes invasive component with higher nuclear grade or more cytoplasm vascular invasion
Stromal response:	desmoplasia retraction artifact inflammation myxoid stroma pseudosarcomatous stroma absent stromal response Reference 8, p. 83.

Recently-emphasized pitfalls in the diagnosis of lamina propria invasive urothelial carcinoma include tangential sectioning, thermal artifact, obscuring inflammation, CIS involving von Brunn nests, deceptively bland urothelial carcinoma, invasion into indeterminate type of muscle, and invasion into adipose tissue within lamina propria [8]. Determination of the type of muscle (muscularis mucosae vs. muscularis propria) invaded by carcinoma can occasionally be difficult due to small tissue sample size, tissue distortion, cautery artifact, poor orientation, fibrosis and inflammation elicited by destructive growth of invasive tumor and even hypertrophy of the normally thin, wispy, and discontinuous muscularis mucosae. This designation of "muscle type indeterminate" is a viable description. As always, the presence or absence of muscularis propria in biopsy and transurethral resection of bladder tumor (TURBT) samples, and presence or absence of carcinoma in identified muscularis propria, should be specified. Only in the last few years has the presence of adipose tissue in all layers of the bladder including lamina propria and muscularis propria (muscle wall or detrusor), been well-documented [30]. So, the presence of carcinoma in fat does not indicate extra-vesical extension.

The level of invasion of carcinoma in pT1 disease is related to patient outcome, with a worse prognosis for tumors that invade beyond the muscularis mucosae (pT1b) [31, 32] or deeply into the subepithelial connective tissue, as quantitated using an ocular micrometer [33]. The WHO 2003 group recommended that some estimate of extent of lamina propria invasion (for example: pT1a - above or into muscularis mucosae vs. pT1b - tumors below) [1, 3] be provided but this is currently not a formal part of the 2002 TNM system, and it is not universally reported, since there is no established method that is consistently applicable and reproducible [3].

Invasion by bladder carcinoma into muscularis propria (muscle wall, detrusor) is an ominous finding where the patient becomes a candidate for aggressive surgical therapy (radical cystectomy) or radiation therapy with or without adjuvant chemotherapy. Current staging issues here have historically been problematic. As discussed above, definitive identification of the thick, compact smooth muscle bundles of the muscularis propria can be difficult in some cases. Substaging of pT2 (pT2a - invasion of "superficial" muscle = inner half vs. pT2b - invasion of "deep" muscle = outerhalf) and distinction of pT2 vs. pT3 can only been done on radical cystectomy specimens, and notTURBT samples. Even in cystectomy specimens it can be a challenge at times to determine extravesical (pT3) spread since the boundary between muscularis propria and its fat is not well-demarcated from perivesical fat. Moreover, this boundary can be distorted, obscured, or obliterated by fibrosis and inflammation associated with infiltrating tumor.

One portion of the 2002 TNM staging system for bladder cancer that requires future clarification is bladder cancer involvement of the prostate. Such involvement is currently staged as pT4a disease, without qualification as to the nature of the involvement. Yet, prognosis for patients with bladder cancer extending into the prostate is highly dependent on bladder stage and prostatic depth of involvement [34, 35, 36, 37] . Patient survival is strongly linked to prostate stromal invasion [35], and prostatic stromal invasion is associated with a better prognosis when the bladder stage is organ-confined [34]. Prostatic stromal invasion via intraurethral spread confers a better survival than extravesical tumor extension into the prostate. It has been recommended that bladder and prostate tumors be staged separately [37], with specification of prostate with non-invasive urothelial carcinoma, prostatic stromal-invasive urothelial carcinoma arising from intraurethral spread, or prostatic stromal-invasive urothelial carcinoma via extravesical spread.

Molecular Classification of Urinary Bladder Neoplasia
Molecular markers hold great promise for the future in classification of urinary bladder neoplasia, but currently there is no molecular parameter that is sufficiently validated and has sufficient prognostic power to have accepted clinical value [1].

Large-scale gene expression profiling of bladder cancer has been reported recently [38, 39] . Objective prediction of classes of bladder tumors using a limited set of genes identified in these studies could have potential clinical utility. In particular, molecular markers would be of substantial value if they could predict which patients with noninvasive (pTa or pTis) bladder cancer would progress to invasive disease and which patients with muscle-invasive tumors will develop metastatic disease after radical cystectomy [40]. General categories of genes that harbor potential capacity for classification include, for example, altered oncogenes, tumor suppressor genes, growth factors, growth factor receptors, and cell cycle-related genes. Specific molecules with abnormalities in expression and/or structure in bladder neoplasia include Her2/neu, epidermal growth factor receptor, H-ras, MDM2, p53, PTEN, RB1, cyclin D1, p15, p16, p21 and p27, to name a few [1]. p53 nuclear protein accumulation and proliferation (MIB-1) index, as assessed by immunohistochemical staining, are two of the more promising markers [1, 41, 42, 43] , but standardization of methodology and quantitation remain as barriers for routine use. However, WHO 2003 concluded that "p53 alterations do not sufficiently well discriminate good and poor prognosis groups in properly staged bladder cancers to have clinical utility" [1].

Reporting of Bladder Neoplasia
In 2003 checklists for reporting on urinary bladder biopsy and cystectomy samples were published by the College of American Pathologists as "Surgical Pathology Cancer Case Summary" protocols [44]. The major categories are summarized here:

Urinary Bladder Biopsy/Transurethral Resection

Histologic type Histologic grade Tumor configuration (papillary, solid/nodule, flat, ulcerated) Muscularis propria (present absent, or indeterminate) pT stage Additional pathologic findings (carcinoma-in-situ, dysplasia, inflammation, therapy changes)

Cystectomy/Cystoprostatectomy/Anterior Exenteration

Tumor site Tumor size Histologic type Histologic grade Pathologic stage (pT and pN) Tumor configuration (papillary, solid/nodule, flat, ulcerated) Margins Venous/lymphatic vessel invasion Direct extension (prostate without stromal invasion, prostate with stromal invasion, adjacent viscera) Additional pathologic findings (carcinoma-in-situ, dysplasia, inflammation, metaplasia, therapy-related changes)

References

1. Pathology and genetics of tumours of the urinary system and male genital organs. In Eble JN, Sauter G, Epstein JI, et al, eds. World Health Organization Classification of Tumours. Lyon: IARC Press, 2003.
2. Mostofi FJ, Davis CJ, Sesterhenn IA, et al: Histological typing of urinary bladder tumours. World Health Organization International Histological Classification of Tumours. Berlin:Springer, 1999.
3. Epstein JI, Amin MB, Reuter VR, et al: The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Am J Surg Pathol 22:1435-1448, 1998.
4. Bostwick DG, Mikuz G: Urothelial papillary (exophytic) neoplasms. Virchows Arch 441:109-116, 2002.
5. Lopez-Beltran A, Martin J, Garcia J, et al: Squamous and glandular differentiation in urothelial bladder carcinomas. Histopathology, histochemistry and immunohistochemical expression of carcinoembryonic antigen. Histol Histopathol 3:63-68, 1988.
6. Young RH, Eble JN: Unusual forms of carcinoma of the urinary bladder. Hum Pathol 22:948-965, 1991.
7. Garcia Garcia F, Garcia Ligero J, Martinez Diaz F, et al: (Bladder carcinoma with osteoclast-type giant cells. A case with a rare presentation. Review of the literature) Acta Urol Esp 27:317-320, 2003.
8. Epstein JI, Amin MB, Reuter VE: Bladder Biopsy Interpretation. Philadelphia:Lippincott Williams and Wilkins, 2004.
9. Amin MB, Gomez JA, Young RH: Urothelial transitional cell carcinoma with endophytic growth patterns. A discussion of patterns of invasion and problems associated with assessment of invasion in 18 cases. Am J Surg Pathol 21:1057-1068, 1997.
10. Young RH, Oliva E: Invasive transitional cell carcinoma of the urinary bladder that may be underdiagnosed: a report of four cases exemplifying the homology between neoplastic and non-neoplastic transitional cell lesions. Am J Surg Pathol 20:1448-1454, 1996.
11. Ro JY, Lapham R, Amin MB: Deceptively bland transitional cell carcinoma of the urinary bladder – further characterization of subtle and diagnostically treacherous patterns of invasion in urothelial neoplasia. Adv Anat Pathol 4: 244-251, 1997.
12. Young RH, Zukerberg LR: Microcystic transitional cell carcinomas of the urinary bladder. A report of four cases. Am J Clin Pathol 96:635-639, 1991.
13. Paz A, Rath-Wolfson L, Lask D, et al: The clinical and histological features of transitional cell carcinoma of the bladder with microcysts: analysis of 12 cases. Br J Urol 74:722-725, 1997.
14. Talbert ML, Young RH: Carcinoma of the urinary bladder with deceptively benign appearing foci – a report of three cases. Am J Surg Pathol 13:374-381, 1989.
15. Murphy WM, Deana DG: The nested variant of transitional cell carcinoma: a clinicopathologic and immunohistochemical study of 44 cases. Mod Pathol 5:240-243, 1992.
16. Drew PA, Furman J, Civantos F, et al: The nested variant of transitional cell carcinoma: an aggressive neoplasm with innocuous histology. Mod Pathol 9:989-994, 1996.
17. Holmang S, Johansson SL: The nested variant of transitional cell carcinoma – a rare neoplasm with poor prognosis. Scand J Urol Nephol 35:102-105, 2001.
18. Cardillo M, Reuter VE, Lin O: Cytologic features of the nested variant of urothelial carcinoma: a study of seven cases. Cancer 99:23-27, 2003.
19. Volmar KE, Chan TY, De Marzo AM, et al. : Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. Am J Surg Pathol 27:1243-1252, 2003.
20. Humphrey PA: Table 14.16: Immunophenotype of prostate vs. transitional cell carcinoma. In: Prostate Pathology. Chicago: ASCP Press, 2003, p. 284.
21. Parker DC, Folpe AL, Bell J: et al. Potential utility of uroplakin III, thrombomodulin, high molecular weight cytokeratin, and cytokeratin 20 in noninvasive, invasive, and metastatic urothelial (transitional cell) carcinomas. Am J Surg Pathol 27:1-10, 2003.
22. Eble JN, Young RH: Benign and low-grade papillary lesions of the urinary bladder: a review of the papilloma-papillary carcinoma controversy and a report of 5 typical papillomas. Sem Diagn Pathol 6:351-371, 1989.
23. Amin MB, Murphy WM, Reuter VE, et al. Controversies in the pathology of transitional cell carcinoma of the urinary bladder. In: Rosen PP, Fechner RE (eds): Reviews in Pathology, Chicago, IL, ASCP Press, 1996, pp. 1-38.
24. Bostwick DG, Ramnani D, Cheng L: Diagnosis and grading of bladder cancer and associated lesions. Urol Clin N Am 26:493-507, 1999.
25. Montironi R, Lopez-Beltran A, Mazzucchelli R, et al : Classification and grading of the non-invasive urothelial neoplasms: recent advances and controversies. J Clin Pathol 56:91-95, 2003.
26. Holmang S, Andius D, Hedelin H, et al: Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy. J Urol 165:1124-1128, 2001.
27. Samaratunga H, Makarov DV, Epstein JI: Comparison of WHO/ISUP and WHO classification of non-invasive papillary urothelial neoplasms for risk of progression. Urology 60:315-319, 2002.
28. van Rhijn BWG, van der Kwast TH, Kirkels WJ, et al: Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol 21:1912-1921, 2003.
29. Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging manual 6^th edition. New York: Springer, 2002, p. 369.
30. Philip AT, Amin MB, Tamboli P, et al. Intravesical adipose tissue: a quantitative study of its presence and location with implications for therapy and prognosis. Am J Surg Pathol 24:1286-90, 2000.
31. Younes M, Sussman J, True LD: The usefulness of the level of the muscularis mucosae in the staging of invasive transitional cell carcinoma of the urinary bladder. Cancer 66:543-548, 1990.
32. Angulo JC, Lopez JI, Grignon D, et al : Muscularis mucosa differentiates two populations with with different prognosis in stage T1 bladder cancer. Urology 45:47-53, 1995.
33. Cheng L, Weaver AL, Neumann RM, et al: Substaging of T1 bladder carcinoma based on the depth of invasion as measured by micrometer: A new proposal. Cancer 86:1035-1043, 1999.
34. Esrig D, Freeman JA, Elmajian DA, et al: Transitional cell carcinoma involving the prostate with a proposed staging classification for stromal invasion. J Urol 156:1071-1076, 1996.
35. Herr HW, Donat SW: Prostatic tumor relapse in patients with superficial bladder tumors: 15-year outcome. J Urol 161:1854-1857, 1999.
36. Schellhammer PF, Bean MA, Whitmore WF Jr.: Prostatic involvement by transitional cell carcinoma: pathogenesis, patterns and prognosis. J Urol 118:399-403, 1977.
37. Njinou Ngninkeu B, Lorge F, Moulin P, et al: Transitional cell carcinoma involving the prostate: a clinicopathological retrospective study of 76 cases. J Urol 169:149-152, 2003.
38. Sanchez-Carbayo M, Socci ND, Lozano JJ, et al: Gene discovery in bladder cancer progression using cDNA microarrays. Am J Pathol 163:505-516, 2003.
39. Dyrskjot L, Thykjaer T, Kruhoffer M, et al: Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet 33:90-96, 2003.
40. Borden LS Jr, Clark PE, Hall MC: Bladder cancer. Curr Opin Oncol 15:227-233, 2003.
41. Kausch I, Bohle A: Molecular aspects of bladder cancer III. Prognostic markers of bladder cancer. Eur Urol 41:15-29, 2002.
42. Helpap B, Schmitz-Drager BJ, Hamilton PW, et al: Molecular pathology of non-invasive urothelial carcinomas (part I). Virchows Arch 442:309-316, 2003.
43. Yan Y, Andriole GL, Humphrey PA, et al. Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors. Cancer 95:1239-1246, 2002.
44. Amin MB, Srigley JR, Grignon DJ, et al: Updated protocol for the examination of specimens from patients with carcinoma of the urinary bladder, ureter, and renal pelvis. Arch Pathol Lab Med 127:1263-1279, 2003.