ReviewMalignant Non-Urothelial Neoplasms of the Urinary Bladder: A Review
Introduction
Non-urothelial neoplasms of the bladder are rare entities in Europe and North America. They are vastly outnumbered by urothelial tumors and account for less than 5% of all vesical tumors combined. In fact, most types of non-urothelial bladder tumors may not be encountered within a lifetime of practicing urology. Despite the low incidence of non-urothelial neoplasms, urologists should be familiar with these tumors and consider them in the differential diagnosis of all bladder masses, in particular those of unusual clinical presentation. The following attempts to provide a comprehensive review of the peer-reviewed literature on primary, malignant, non-urothelial bladder tumors according to the histological classification by the World Health Organization (WHO) (Table 1) [1]. It summarizes the available evidence on the etiology, diagnosis and therapeutic management of these rare malignant masses that, with exception of schistosomiasis-related squamous cell carcinoma, is mainly derived from small retrospective case series and case reports. While pseudo-inflammatory tumors are histologically benign, they may closely mimic sarcomatous neoplasms and should therefore be considered in the differential diagnosis.
Section snippets
Squamous cell carcinoma
Second to urothelial carcinoma, squamous cell carcinoma (SCC) is the most prevalent epithelial neoplasm of the bladder, accounting for an approximate 3–5% of bladder tumors in Western countries [2]. Microscopically the tumor may be well differentiated, consisting of well defined islands of squamous cells with keratinization, prominent intercellular bridges, and minimal nuclear pleomorphism, or poorly differentiated, with marked nuclear pleomorphism and only focal squamous differentiation (Table
Non-schistosoma-related SCC
Pure SCC of the bladder is a rare finding in Western countries and is to be distinguished from urothelial bladder cancer with partial squamous differentiation, a relatively common finding in radical cystectomy specimens. In a large recent cystectomy series from the Memorial Sloan Kettering Cancer Center (MSKCC), only 2.8% of patients demonstrated pure SCC [5]. While a number of etiological factors have been implicated in the pathogenesis of SCC (Table 3), the most relevant common factor appears
Schistosoma-related SCC
In areas where schistosoma is endemic, bladder cancer is a common disease, and SCC constitutes the most common histological type [16]. Compared to urothelial bladder cancer, the age of presentation is lower, affecting mainly men in their fifth decade of life. Schistosoma-related SCC may be regarded a potentially preventable disease, affecting mainly patients who are repeatedly exposed and re-infected by the schistosoma parasite, that completes it life cycle by depositing its eggs into the
Adenocarcinoma
Pure adenocarcinoma of the bladder represents the third most common type of epithelial tumor comprising 0.5–2.0% of all bladder tumors [19]. It occurs more frequently in geographic regions where schistosomiasis is endemic [20] and is the most common tumor arising in the bladder of exstrophy patients, who have a reported 4% life-time risk for developing this type of malignancy [21]. While there is some variability in the defining adenocarcinoma in the literature, the pathological hallmark of
Small cell carcinoma
Primary small cell or neuroendocrine carcinoma of the bladder is an extremely uncommon entity and accounts for less than 0.5% of bladder tumors or approximately 130 reported cases [34], [35]. Microscopically, it resembles small cell carcinoma of the lung, composed of a population of relatively uniform cells with scant cytoplasm and hyperchromatic nuclei. Extensive necrosis and frequent mitotic figures are common [3]. The histogenesis of small cell carcinoma of the bladder is uncertain; both
Bladder sarcoma
While all types of non-epithelial bladder tumors are extremely rare, malignant soft tissue tumors represent the most common histological type. A recent review of the literature identified a total of 192 reported cases of adult bladder sarcoma, of which 50% were leiomyosarcomas, 20% rhabdomyosarcomas, and the remainder angio-, osteo- and carcinosarcoma [38]. Leiomyosarcomas, the most common type of sarcoma in adults, are histologically characterized by interwoven bundles of spindle shaped cells.
Carcinosarcoma and sarcomatoid tumors
The term carcinosarcoma describes a rare biphasic type of primary bladder tumor composed of an intimate admixture of both malignant epithelial (carcinoma) and malignant soft tissue elements (sarcoma). Meanwhile, the term sarcomatoid tumor has been used to describe a malignant primarily spindle cell type tumor with epithelial differentiation [41]. In light of the controversy over these definitions, the Mayo Clinic reviewed their experience of 15 patients with carcinosarcoma and 26 patients with
Paraganglioma
Paragangliomas are extraadrenal neoplasms of neural crest derivation that are termed pheochromocytoma if hormonally active. Bladder pheochromocytomas are exceedingly rare, accounting for less than 0.05% of bladder tumors. Histologically they are characterized by cells arranged in discrete nests (“Zellballen”) separated by a prominent sinusoidal network. They are believed to arise from embryonic rests of chromaffin cells in the sympathetic plexus of the detrusor muscle and represent
Inflammatory pseudotumors
These represent rare, spindle-cell type neoplasms, which are also referred to as pseudosarcomatous tumors or myofibroblastic tumors [46]. Although these tumors are benign, they combine pathological features of both inflammatory and neoplastic processes that can make the differential diagnosis to sarcoma extremely difficult. The histogenesis of inflammatory pseudotumors remains largely unclear. A subset of these tumors present within 3 months of a surgical procedure [47] and are referred to as
Melanoma
Melanoma of the bladder is most commonly a secondary presentation of patients with widespread metastatic melanoma originating from the skin. However, rare cases of primary melanoma of the bladder and female urethra, reportedly the most frequent location of primary melanoma of the urinary tract, have been described [39], [49]. In such cases, a detailed patient history, careful examination of the patient’s skin and evaluation for other viszeral primary sites are necessary to confirm the primary
Lymphoma
Most frequently, bladder lymphoma reflects widespread metastatic disease of systemic hematological disease. However, rare primary lymphomas of the bladder occur. Histologically, these tumors consist of a diffuse, infiltrative proliferation of lymphoid cells surrounding and permeating normal structures rather than replacing them [3]. A recent review identified 84 cases of primary lymphoma [53] that were more common in women than men (3:1) and in large proportion represented so-called Lymphoma of
Conclusions
Primary non-urothelial bladder tumors often present a diagnostic and therapeutic challenge. While this review provides a framework to direct patient management, it appears important to account for the fact that available evidence on many of these rare malignancies stems from small, retrospective case series. As in other rare tumors it will likely take the concerted effort of many institutions linked together by a national or international tumor registry to develop and evaluate effective
References (61)
- et al.
Disease specific survival as endpoint of outcome for bladder cancer patients following radical cystectomy
Eur. Urol.
(2002) - et al.
Incidence of squamous cell carcinoma in patients with long-term catheter drainage
J. Urol.
(1985) - et al.
Malignant vesical tumors following spinal cord injury
J. Urol.
(1987) - et al.
Bladder cancer and squamous metaplasia in spinal cord injury patients
J. Urol.
(1977) - et al.
Screening cystoscopy and survival of spinal cord injured patients with squamous cell cancer of the bladder
J. Urol.
(1997) - et al.
Role of chronic catheterization in the development of bladder cancer in patients with spinal cord injury
Urology
(1999) Transitional cell carcinoma in patients with spinal cord injury: a high risk malignancy?
Urology
(2002)- et al.
The use of urine cytology for diagnosing bladder cancer in spinal cord injured patients
J. Urol.
(1997) - et al.
Squamous carcinoma of the bladder: treatment by radical cystectomy
J. Urol.
(1976) - et al.
Preoperative irradiation and radical cystectomy for stages T2 and T3 squamous cell carcinoma of the bladder
J. Urol.
(1990)
Radical cystectomy for carcinoma of the bladder: critical evaluation of the results in 1,026 cases
J. Urol.
Primary adenocarcinoma of bladder
Urology
Intestinal metaplasia is not a strong risk factor for bladder cancer: study of 53 cases with long-term follow-up
Urology
Malignant urachal lesions
J. Urol.
Adenocarcinoma of urinary bladder: classification and management
Urology
Urachal cancer: role of conservative surgery
Urology
Multimodality management of urachal carcinoma: the M.D. Anderson Cancer Center experience
J. Urol.
Prognostic factors in urachal adenocarcinoma. A study in 41 specimens of DNA status, proliferating cell-nuclear antigen immunostaining, and argyrophilic nucleolar-organizer region counts
Hum. Pathol.
Signet-ring cell adenocarcinoma of bladder
Urology
Leiomyosarcoma in urinary bladder after cyclophosphamide therapy for retinoblastoma and review of bladder sarcomas
Urology
Adult urological sarcoma
J. Urol.
Carcinosarcoma and sarcomatoid carcinoma of the bladder: clinicopathological study of 41 cases
J. Urol.
Durable complete remission of metastatic sarcomatoid carcinoma of the bladder with cisplatin and gemcitabine in an 80-year-old man
Urology
Extra-adrenal pheochromocytoma
J. Urol.
Diagnostic localization of malignant bladder pheochromocytoma using 6-18F fluorodopamine positron emission tomography
J. Urol.
Pheochromocytoma
Urology
Inflammatory pseudotumor and sarcoma of urinary bladder: differential diagnosis and outcome in thirty-eight spindle cell neoplasms
Mod. Pathol.
Primary malignant melanoma of the bladder: immunohistochemical study of a new case and review of the literature
J. Urol.
Racial variation in the incidence of squamous cell carcinoma of the bladder in the United States
J. Urol.
Primary neoplasms in vesical diverticula: report of 10 cases
J. Urol.
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