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  Table of Contents  
Year : 2019  |  Volume : 56  |  Issue : 3  |  Page : 254-260

A clinicopathological and immunohistochemical study of non-urothelial bladder tumours

Department of Pathology, Bhopal Memorial Hospital and Research Centre (Under Department of Health Research), Bhopal, Madhya Pradesh, India

Date of Web Publication19-Jul-2019

Correspondence Address:
Avinash Gupta
Department of Pathology, Bhopal Memorial Hospital and Research Centre (Under Department of Health Research), Bhopal, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_459_17

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 » Abstract 

BACKGROUND: Non-urothelial bladder tumors (NUBTs) are uncommon accounting for approximately 10% of the total urinary bladder tumors while 90% are urothelial in origin. There are very limited comprehensive studies on NUBTs.
AIMS AND OBJECTIVES: The objectives of the study were to analyze the clinicopathological and immunohistochemical features of NUBTs.
MATERIALS AND METHODS: This is a retrospective study of NUBTs diagnosed over a period of 9 years. Patients' files were retrieved from the archives. Gross and microscopic features were recorded. Simple percentage and frequencies were used to interpret the data.
RESULTS: A total 16 cases (10.8% of all bladder tumors) of NUBT were found. Patients' ages ranged from 19 to 87 years with a male: female ratio of 4.3:1. The most common presenting symptom was gross hematuria (81.2%), and the most common location was posterolateral bladder wall. Muscle invasion was seen in 81.2% of cases, and large areas of necrosis were observed in 62.5%. There were two cases of squamous cell carcinoma, five cases each of adenocarcinoma (four secondary and one urachal) and mesenchymal tumors (four malignant and one benign), two cases of amyloid, and one case each of plasmacytomas and paraganglioma. Large areas of necrosis and muscle invasion were noted in high-grade and advanced staged tumors. In all, 43.7% had poor survival.
CONCLUSION: NUBTs present with similar clinicoradiological findings; however, their histological features along with immunohistochemistry help in the definite diagnosis. One should be aware of these tumors as they frequently present diagnostic and therapeutic challenge. Most of these neoplasms present at an advanced stage. Large or multicentric randomized controlled studies are needed to know the exact behavior and prognosis of these tumors.

Keywords: Hemangioma, hematuria, leiomyosarcoma, squamous cell, urinary bladder

How to cite this article:
Kaur S, Gupta A, Gulwani HV. A clinicopathological and immunohistochemical study of non-urothelial bladder tumours. Indian J Cancer 2019;56:254-60

How to cite this URL:
Kaur S, Gupta A, Gulwani HV. A clinicopathological and immunohistochemical study of non-urothelial bladder tumours. Indian J Cancer [serial online] 2019 [cited 2021 Nov 27];56:254-60. Available from: https://www.indianjcancer.com/text.asp?2019/56/3/254/263035

 » Introduction Top

Worldwide, cancer of the urinary bladder (UB) accounts for approximately 7% of cancer in men and 3% of cancer in women.[1] As per Indian cancer registry data, it is the ninth most common cancer in men accounting for 3.9% of all cancers.[2] About 95% are of epithelial origin, the remaining being mesenchymal tumors.[3] Transitional cell (urothelial) carcinoma (TCC) is the most common of all primary tumors of this organ comprising approximately 90%. Cases of squamous cell carcinoma (SCC) (5%),[4] primary adenocarcinoma (AC) (2%),[4] small cell carcinoma, and sarcomas are encountered much less frequently. Carcinoma of the bladder affects men more than women in a ratio of 3–4:1.[5] In 85% of cases, the most common presenting symptom is painless hematuria.[6] Urine cytology may be performed; however, diagnosis usually requires cystoscopy and biopsy. These two have been the gold standards in the diagnosis of bladder cancers and in the follow-up period. This study is an attempt to present a comprehensive data of clinical and histomorphology of various NUBTs encountered in our institute.

 » Materials and Methods Top

Study design

This is a retrospective study carried out in the Department of Pathology, Bhopal Memorial Hospital and Research Centre (BMHRC), Bhopal, Madhya Pradesh, India. BMHRC is one of the major referral hospitals in and around Bhopal. The study was approved by the Institutional Ethics Committee. All cases of NUBTs that were diagnosed between January 2008 and December 2016 were included for analysis. Seven radical cystectomies, one partial cystectomy, six TURBT chips (both superficial and deep biopsies), and two small cystoscopic biopsy specimens were retrieved. The patients' files were retrieved to record the age, sex, presenting complaints, radiological, and cystoscopic findings including size and location of tumor. The gross and microscopic features of the specimens were recorded. Histopathology slides [hematoxylin and eosin–stained slides, special stains, and immunohistochemistry (IHC)] of all the cases were reviewed. Wherever required, the faded slides were restained. Histological type, grade, muscle invasion, necrosis, and other associated findings of all the tumors were recorded. The tumors were diagnosed according to World Health Organization classification.[1] Simple percentage and frequencies have been used to interpret the data.

 » Results Top

A total of 148 bladder tumors were retrieved which included 132 cases of TCCs (89.2%) and 16 cases (10.8%) of NUBT. Males predominated with an M: F ratio of 4.3:1. Patients' ages ranged from 19 to 87 years. The most common presenting symptom was gross hematuria (81.2%). Other presenting symptoms were lower abdominal mass and pain. Irritable bladder and urinary tract infection were observed in some patients. The most common location of these tumors was posterolateral wall of UB. Muscle invasion was seen in 81.2% of cases (n = 13), and large areas of necrosis were observed in 62.5% (n = 10). Distribution of tumors, clinicopathologic characteristics, and their follow-up are shown in [Table 1] and [Table 2].
Table 1: Distribution of non-urothelial tumors

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Table 2: Clinicopathological features and follow-up of patients with nonurothelial tumors

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In this study, two cases were of well-differentiated SCC (12.6%). Radical cystectomy was done in both the cases. One case was of a 60-year-old woman who presented with a lump in the lower abdomen. Cystoscopically, the growth was ulceroinfiltrative and was present in the left posterolateral wall. The other case was of a 69-year-old man who presented with hematuria. On cystoscopy, a sessile proliferative tumor was located in the right lateral wall. Both these tumors were composed of malignant squamous cells that were lying in sheets [Figure 1]a. In addition, keratin pearls along with many polylobated giant cells were present. Necrosis was seen in the second case. Squamous metaplasia was present in the adjacent bladder mucosa. Urothelial element was absent. Tumor invaded deep muscularis propria (pT2) in both the cases. On IHC, tumor cells were positive for Pan-Cytokeratin (CK) and negative for CK-7 and CK-20. There was no evidence of schistosomiasis or bladder stone.
Figure 1: (a) Squamous cell carcinoma, (b) urachal mucinous adenocarcinoma, (c) secondary colonic adenocarcinoma, (d) secondary prostatic adenocarcinoma (inset: Prostate-specific antigen positive), (e) leiomyosarcoma (inset: Vimentin positive and Pan-cytokeratin negative), (f) myxoid leiomyosarcoma (Inset: Smooth muscle actin positive)

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Five cases of AC were found in this study. One was primary AC (6.2%) of urachal origin and the remaining four were metastatic AC. Single case of primary urachal AC occurred in a 63-year-old man, who presented with hematuria and lower abdominal lump. Radical cystoprostatectomy with en bloc resection of urachus and umbilectomy was done. Grossly, an ulceroinfiltrative growth was seen involving both urachus and dome of UB. The tumor was very fragile and had mucin pools in it. Histologically, it was mucinous AC with presence of intra- and extracellular mucin (mucicarmine positive) and many signet ring cells. Cystitis glandularis and intestinal metaplasia were not found [Figure 1]b.

Four cases of secondary AC (25%) were found. Special attention was paid to identify primary site elsewhere. Of the four cases, one was an operated case of carcinoma colon (42 years/woman) and the other (19 years/man) was a known case of postchemotherapy rectosigmoid AC where the bladder tumor was detected during follow-up. Both presented with complaint of gross hematuria. Cystoscopically, one had mucosal thickening of the posterolateral wall and the other had exo- and endophytic growth in the posterior bladder wall. Microscopically, both cases revealed well-differentiated AC with unremarkable transitional epithelium. There were well-formed glands that were lined by columnar malignant epithelial cells [Figure 1]c. The remaining two cases (87 and 63 years/males) presented with hematuria and irritable bladder symptoms. Cystoscopically, in both the cases the tumor was present in the trigone and bladder neck. Histopathological sections revealed malignant epithelial cells lying in sheets and glandular configuration. The cells had round to oval, large hyperchromatic nuclei, prominent nucleoli, and scanty cytoplasm. The overlying transitional epithelium was intact [Figure 1]d. On IHC, tumor cells were Prostate specific antigen (PSA) and alpha-methylacyl-CoA racemase (AMACR)-positive. Raised serum PSA levels (more than 40 ng/mL) and clinicoradiological findings confirmed primary in the prostate. Invasion of muscle layer and necrosis were seen in all the four cases.

There were four cases of mesenchymal tumors of UB (25%) including two cases of high-grade leiomyosarcoma (LMS), one case each of myxoid LMS and undifferentiated pleomorphic sarcoma. Radical cystectomy was done in all. Extensive sampling was done to rule out epithelial component.

One case of high-grade LMS occurred in a 78-year-old woman who presented with hematuria and had a polypoidal growth in the posterior wall of the bladder (6.5 × 3 cm in size). Microscopic findings revealed chiefly ulcerated mucosa; however, in focal areas benign transitional epithelium was present. Just beneath the epithelium, malignant spindle cells that were chiefly arranged in fascicular pattern were seen, whereas in other areas they were arranged haphazardly [Figure 1]e. Marked nuclear pleomorphism along with multinucleated bizarre tumor giant cells and many atypical mitotic figures (6–8/10 hpf) were observed. There were large areas of necrosis and hemorrhage. Tumor was invasive and also metastasized to the regional lymph nodes.

The other case of high-grade LMS was a 60-year-old man. He had a polypoidal growth in the left posterolateral wall (7.5 × 5.5 cm). Histologically, the tumor cells were spindle-shaped and arranged in fascicular pattern. The cells had cigar-shaped nuclei with blunt ends and moderate amount of eosinophilic cytoplasm. Moderate anisonucleosis and more than 5/10 hpf mitotic figures were present. Areas of hemorrhage, necrosis, and focal myxoid change were seen. Tumor cells infiltrated the muscle layer. In both cases of LMS, the tumor cells were immunoreactive for SMA and vimentin [[Figure 1]e, inset], whereas they were nonreactive for Pan-CK [[Figure 1]e, inset], CK-7, CK-20, CD68, CD99, CD34, and Desmin.

A single case of myxoid LMS was found in a 68-year-old man. There was a polypoidal growth in the posterior wall (5 × 4 × 3 cm in size) of the bladder. Cut section showed gelatinous areas. Microscopically, the tumor was hypocellular compared with conventional LMS. Tumor cells were spindle-shaped and surrounded by myxoid matrix. These cells were arranged in short fascicles and had mild nuclear pleomorphism along with moderate amount of eosinophilic cytoplasm [Figure 1]f. Focal areas of calcification and necrosis were seen. Tumor was invasive and infiltrated up to the serosa. Tumor cells were immunoreactive for vimentin and SMA [[Figure 1]f, inset] and negative for Pan-CK, EMA, and Desmin.

One case of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma inflammatory type was found. The patient was a 45-year-old man and presented with hematuria and abdominal lump. A large (11 × 8 × 2 cm) proliferative friable growth attached to the posterior wall of the bladder was noted. On microscopy, the tumor was densely cellular, composed of mixture of pleomorphic spindle cells that were arranged in storiform pattern and diffuse sheets of round to polygonal cells having hyperchromatic nuclei, eosinophilic cytoplasm, and prominent nucleoli. Many of these cells had eccentrically placed nuclei with abundant eosinophilic cytoplasm [Figure 2]a and [Figure 2]b. Numerous atypical mitotic figures and apoptosis were noted. There were large areas of necrosis, hemorrhage, and dense mixed inflammatory cell infiltration. Muscle layer involvement, vascular invasion, and lymph node metastases were present. Tumor cells were strongly positive for vimentin and focally for CD68 [[Figure 2]b, inset] and α-1 antichymotrypsin. These were negative for Pan-CK, Desmin, HMB-45, S-100, and CD34.
Figure 2: (a and b) Malignant fibrous histiocytoma (b) (inset: CD68 positive), (c) hemangioma [inset: Muscle invasion], (d) amyloid, (e) plasmacytoma (inset: Kappa positive and Pan-cytokeratin negative), (f) paraganglioma (inset: Synaptophysin positive)

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We have found one case of hemangioma (6.2%, benign mesenchymal tumor). The patient was a 33-year-old man and presented with gross hematuria. Cystoscopic findings revealed multiple irregular grayish black to reddish nodular lesions. Partial cystectomy was done. Histologically, the tumor was composed of variable sized thin-walled vascular channels that were filled with red blood cells [Figure 2]c. Muscle layer was involved [[Figure 2]c, inset].

We have found two cases of amyloidosis. Both were man in the fifth decade and presented with complaint of gross hematuria. One patient was a known case of non-Hodgkin's lymphoma B-cell type and was on chemotherapy; hence, the diagnosis of secondary amyloidosis was made. Imaging findings revealed abdominal lymphadenopathy and a 1.5 × 1.2 cm mass with lobulated contours involving the posterior wall of the bladder. Kidneys and other organs were unremarkable. The other patient had no history of other system involvement and was diagnosed with primary amyloidosis. He had a 4.5 × 2.3 cm polypoidal trigonal mass that was extending to the right lateral bladder wall. TURBT was done. In both the cases, amorphous extracellular eosinophilic deposits were seen in the lamina and blood vessels [Figure 2]d. The overlying urothelium was unremarkable. Additional findings include focal calcification, foreign body giant cell reaction, and mixed inflammatory infiltrate. Presence of amyloid was confirmed by Congo red stain. There was no evidence of muscle invasion and necrosis.

A single case of plasmacytoma in a 60-year-old man was reviewed. He presented with lump in the abdomen. Cystoscopically, there were two sessile mass of 6 × 6 cm and 3 × 3 cm size involving the left lateral wall and posterior wall, respectively. Histologic examination showed sheets of neoplastic plasma cells involving muscle layer as well [Figure 2]e. The plasma cells showed lambda light chain restriction [[Figure 2]e, inset] and negative for LCA and Pan-CK [[Figure 2]e, inset]. To exclude solitary plasmacytoma of bladder, bone marrow examination was done and it revealed increased plasma cells (more than 40%). M-spike was noted on serum protein immunoelectrophoresis. This was a case of multiple myeloma which presented initially as a bladder mass.

One case of paraganglioma was found in a 52-year-old man who presented with hematuria. The patient was nonhypertensive. Cystoscopy-guided small biopsy was received and microscopic findings revealed nests and sheets of epithelioid tumor cells below the unremarkable benign transitional epithelium of the bladder. These cells had round hyperchromatic, mildly pleomorphic nuclei, and moderate to abundant eosinophilic to vacuolated cytoplasm [Figure 2]f. Muscle layer was also involved. The cells were positive for synaptophysin [[Figure 2]f, inset] and negative for CK-7, CK-20, HMB-45, and PSA. Provisional diagnosis of paraganglioma was made on the basis of IHC. Because the tissue was small, a repeat biopsy was advised but the patient did not follow up.

 » Discussion Top

Approximately 95% of malignant tumors arising in the UB are of epithelial origin, and 90% of these are TCCs.[5] In this study, the nonepithelial tumors comprise 6% of total bladder tumors (n = 148) and 56.2% of NUBTs (n = 16), and mesenchymal tumors (4 malignant and 1 benign) constitute 3.3% of all bladder tumors and 31.2% of NUBT. LMS is the most common type. As per the literature, NUBTs are rare and frequently present a diagnostic and therapeutic challenge. The incidence is more common in males and occurs in the fifth and sixth decades. Urothelial carcinoma has a great propensity for divergent differentiation, which may lead to squamous, glandular or neuroendocrine or sarcomatous differentiation. Specific terms such as squamous cell carcinoma, adenocarcinoma, sarcoma, and so on are reserved for bladder tumors that are entirely composed of that particular differentiation and are without urothelial component. Most of the NUBTs have a muscle invasive disease.

SCC constitutes 2%–7% of bladder cancer except in Middle East along the Nile Valley where as a consequence of endemic schistosomiasis, they are the most common form of bladder cancer.[5] Based on the etiology of cancer, SCC can be further classified as bilharzial (Schistosoma haematobium) and non-bilharzial.[7],[8] The association between chronic bladder irritation and SCC has been postulated, which includes chronic or recurrent urinary tract infection, chronic indwelling urinary catheter, neurogenic bladder, bladder calculi, foreign bodies, prolonged exposure to cyclophosphamide,[9] and exostrophy of UB.[10] A recent study of the SEER database by Scosyrev et al.[11] has shown that SCC was more aggressive than urothelial cancer after adjusting for common prognostic factors, such as stage. In this study, both the tumors were well-differentiated non-bilharzial SCC and were invasive in nature.

AC is the third most common type of bladder cancer comprising 0.5%–2.0% cases of all bladder tumors.[12] Secondary ACs are more common.[13] It is more frequent in males in their sixth decade of life, presenting with hematuria and symptoms attributable to bladder irritation. Primary ACs are derived from the urothelium but exhibit pure glandular phenotype. These are further classified as urachal (U) and non-urachal (NU) based on the criteria described by Grignon et al.[14] Features which favor the diagnosis of urachal ACs are tumor of the dome, absence of cystitis glandularis cystica, primary involvement of muscle or deeper structures, an intact or ulcerated epithelium, presence of suprapelvic mass, sharp demarcation between tumor and normal surface epithelium, presence of urachal remnants, and tumor branching into the space of Retzius.[15],[16] Results from the SEER database show that urachal cancer makes up about 10% of all ACs of the bladder.[17] The importance of differentiating urachal (U) from non-urachal (NU) tumors is controversial. In our study, no case of primary AC was found; however, there was one case of urachal AC, mucinous type which was locally infiltrating the bladder wall. Secondary AC involves the bladder either by direct extension or by metastases from a distant site. The common origins include the colon, prostate, endometrium, cervix, breast, and lung. In this study, four secondary ACs were found, two were known cases of carcinoma colon, and two had prostatic AC (direct invasion). Diagnosis was made after considering the clinicoradiological findings, raised PSA levels, and IHC markers.

Sarcoma is the most frequent mesenchymal malignancy of the bladder [18] with LMS being the common entity. The most common clinical presentation is gross hematuria (81%).[19] These are often large and polypoid; they are unencapsulated and usually exhibit full-thickness involvement of the bladder wall. Histologically, well-differentiated tumor has interlacing bundles and fascicles and elongated cells with eosinophilic cytoplasmic processes and hyperchromatic nuclei with or without small nucleoli.[20] Grading of LMS is based on the degree of cytologic atypia. Low-grade LMS exhibits mild to moderate cytologic atypia and has mitotic activity less than 5 mitoses per 10 HPF. In contrast, high-grade LMS shows marked cytologic atypia, and most cases have greater than 5 mitoses per 10 HPF.[1] Lee et al.[21] reviewed 20 cases of bladder LMS, focusing on the criteria for distinguishing leiomyoma from LMS, and the subdivision of the latter into low- and high-grade sarcomas, largely based on mitotic activity. In an another review study by Hamadalla et al.,[22] these tumors are rare and occur in older adults of either sex and are characterized by an aggressive behavior. In this study, similar findings with aggressive course (less than 1 year survival) were seen as both the cases were high-grade LMS. LMS has a poor prognosis, especially if they are of high grade and stage.[1]

Myxoid LMS is one of the morphologic variants of LMS. It is composed of malignant smooth muscle cell proliferation with an abundant myxoid matrix. It is characterized by low cellularity with moderate number of thin-walled blood vessels and low mitotic index.[23] Because of the hypocellularity and the bland cytological aspect, it represents a diagnostic challenge. For an accurate result, multivariate diagnosis criteria are taken into consideration, such as mitotic index value, the grade of nuclear atypia, and the presence of tumor cell necrosis. Immunohistochemically, they are similar to conventional LMS. These tumors occur in older adults of either sex and are characterized by an aggressive behavior. In this study, one patient of myxoid LMS died after 6 months of diagnosis.

Pleomorphic undifferentiated sarcoma (also called as pleomorphic malignant fibrous histiocytoma) is an extremely rare entity.[1],[24] The tumor appears in male in the sixth decade and presents with manifestations similar to those of other mesenchymal bladder tumors. They are rapidly progressive and have very poor prognosis. Pleomorphic undifferentiated sarcoma must be separated from sarcomatoid urothelial carcinoma and reactive spindle cell proliferations of the bladder [1] as the latter two stain positively for Pan-CK. Microscopically, there is no epithelial component. It is often reactive for vimentin, α-1 antichymotrypsin, and focally reactive for CD68.[1] In our case, the tumor cells showed similar IHC profile. The patient refused any form of treatment and succumbed 4 months later.

In this study, all the four cases of sarcomas had muscle invasion and large areas of necrosis. In two cases, lymph node involvement was noted.

Hemangioma is a very rare primary tumor of the bladder representing only 0.6% of all bladder tumors [25] and occurs predominantly in patients younger than 30 years, with a slight male predominance. The chief clinical symptom is recurrent, isolated hematuria. Other symptoms include suprapubic pain due to vesical irritation and urinary retention.[26] It is most likely congenital in origin, arising from embryonic angioblastic stem cells.[27] The majority of hemangiomas are solitary, small, and cavernous, with a predilection for the dome, posterior wall, and trigone of the bladder. Hemangiomas are differentiated from Kaposi sarcoma and angiosarcoma by lack of cytologic atypia and exuberant granulation tissue. Biopsy with or without fulguration is the effective conservative treatment. In a study of 19 patients by Cheng et al.,[28] none of the patients developed recurrence in the mean follow-up period of 6.9 years. We had one case of cavernous hemangioma (0.6% of all bladder tumors and 6.2% of NUBTs) involving the right lateral wall of the bladder. He was treated with partial cystectomy followed by fulguration. After 2 years of recurrence-free period, the patient was lost to follow-up.

Amyloidosis consists of amyloid, a pathologic proteinaceous substance, deposited in the extracellular space, in one or more body sites. The onset of the disease is often in the sixth to eighth decades of life similar to that of urothelial carcinoma.[29] Its appearance on imaging and on cystoscopy also misleads the diagnosis to malignancy.[30] Accurate diagnosis depends on the demonstration of amyloid deposits either by Congo red staining or by scintigraphy with radiolabeled serum amyloid P (SAP) component.

Primary amyloidosis of bladder is rare. The lesion appears throughout adulthood and is equally common in both sexes. In most cases, the deposits are limited to the bladder, but in some cases ureters and urethra are also involved. Hematuria is almost always the presenting symptom.[23] On cystoscopy, the lesions range from sessile and ulcerated to nodular or polypoid, and often are mistaken for carcinoma. Histologically, amyloid deposits are predominantly in the lamina propria and muscularis propria. Vascular involvement is less prominent. Foreign body giant cell reaction may be present adjacent to the deposits, and rarely the deposits become calcified. Secondary involvement of the bladder is also rare in systemic amyloidosis.[23] Amyloidosis is associated with various malignancies, particularly multiple myeloma, medullary carcinoma of the thyroid, Hodgkin's disease, and renal cell carcinoma.[31] The treatment is usually conservative with TURBT. Long-term follow-up with imaging and cystoscopy is required. In this study, we have encountered two cases of amyloidosis. One was primary amyloidosis and the other was secondary amyloidosis (known case of non-Hodgkin's lymphoma).

Plasmacytoma of the UB is a rare extramedullary manifestation of plasma cell dyscrasia. In this study, the patient presented with intravesical mass and was subsequently diagnosed as multiple myeloma. Hence, one must be careful while diagnosing a tumor with plasmacytoid morphology. To differentiate it from anaplastic TCCs (plasmacytoid variant), IHC, serum immunoelectrophoresis, bone marrow examination, and skeletal survey should be performed as the prognosis and course of treatment of both the entities are different.

Paraganglioma is a rare neoplasm that accounts for <0.06% of all UB tumors and 6% of all extra-adrenal pheochromocytomas. It arises from chromaffin tissue of the sympathetic nervous system within the layers of the bladder wall.[32] The tumor tends to occur in young patients (mean 45 years) with an M:F ratio of 1:3. Based on catecholamine secretion, these are classified into functional and nonfunctional types. The majority (80%) of these are functional type and secrete catecholamines resulting in symptoms such as paroxysmal hypertension, palpitations, micturitional syncope, and headache.[33] Nonfunctional types lack symptoms of catecholamine excess and, therefore, are often misdiagnosed as urothelial cancer during preoperative evaluation.[34],[35] Since histomorphological overlap occurs with urothelial carcinoma and its variants, especially the nested variant, a careful assessment on microscopy coupled with ancillary immunohistochemical methods prevent misdiagnosis. They reveal immunoreactivity for neuroendocrine markers.[32] Other differential diagnosis includes granular cell tumor, metastatic large cell neuroendocrine tumor, and malignant melanoma. Distinction from TCC is imperative as management and prognosis vary markedly.

Most of the cases in this study had high grade and advanced disease with poor survival [Table 1]. This study has a small cohort size, and therefore further prospective studies are needed to develop tailored treatment paradigms. Until then, urologists must maintain a high index of clinical suspicion for aggressive disease in patients who present with nonurothelial histology.

 » Conclusion Top

Morphologically, various different tumors may arise in the UB other than urothelial neoplasms. Most of these are rare and present at an advanced stage and grade. Sarcomas are usually muscle invasive and have large areas of necrosis. Before rendering a diagnosis of NUBT, exclude the history of a high-grade urothelial carcinoma or of concurrent urothelial component. One should be aware of these lesions as they present with similar clinicoradiological findings but have different prognostic and therapeutic implications. Combined approach including adequate clinical information, histomorphology with special stains, and IHC can lead to definite diagnosis. Because of the very low incidence, little knowledge about the natural history, prognosis of the tumor, and no consensus about the standard treatment, large multicentric randomized controlled studies are required.

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Conflicts of interest

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 » References Top

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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