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Year : 2006  |  Volume : 22  |  Issue : 4  |  Page : 378-380

The nested variant of transitional cell carcinoma of urinary bladder: An aggressive tumour with a bland morphology

1 Department of Urology, Christian Medical College, Vellore, Tamilnadu, India
2 Department of Pathology, Christian Medical College, Vellore, Tamilnadu, India

Correspondence Address:
Nitin S Kekre
Department of Urology, Christian Medical College, Vellore, Tamilnadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-1591.29133

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How to cite this article:
Krishnamoorthy S, Korula A, Kekre NS. The nested variant of transitional cell carcinoma of urinary bladder: An aggressive tumour with a bland morphology. Indian J Urol 2006;22:378-80

How to cite this URL:
Krishnamoorthy S, Korula A, Kekre NS. The nested variant of transitional cell carcinoma of urinary bladder: An aggressive tumour with a bland morphology. Indian J Urol [serial online] 2006 [cited 2023 Mar 24];22:378-80. Available from:

The nested variant of transitional cell carcinoma (NV-TCC) is a relatively rare neoplasm of the urinary bladder. So far, about 80 cases have been reported in the literature.[1] Irregular nests and tubules of TCC infiltrating the lamina propria, with no involvement of the mucosal layer characterize the disease. We report a case of a 46-year-old woman, with a large bladder tumor, occupying almost the entire bladder. She presented with an episode of urinary retention with no history of hematuria. This case is being reported due to its rarity, unusual histology and its prognostic significance emphasizing the need to distinguish it from the classic TCC.

   Case Report Top

A 46-year-old woman had complaints of interrupted stream of urine for two years. She developed acute retention of urine in April 2006. Further evaluation after catheterization revealed a large bladder tumor. There was no prior history of hematuria or urinary tract infections. She was not a known hypertensive or a diabetic. Physical examination was unremarkable. Her PCV was 26% and urine microscopy revealed 12-15 red blood cells per high power field. Liver function tests and Skiagram chest were normal. Cystoscopy revealed a solid 10 x 10 cm pedunculated lesion arising from the right lateral and the anterior wall of the bladder. It was a rounded, mobile, well-circumscribed tumor with a smooth surface. The mucosa over the mass lesion and the adjoining bladder surface appeared intact. Right ureteric orifice was not seen and the left ureteric orifice appeared normal. The tumor was bimanually palpable and mobile. She underwent transurethral resection of tumor and the biopsy was reported as NV-TCC with marked atypical epithelial proliferation.

   Discussion Top

Radiological discussion

An ultrasound abdomen showed bilateral mild hydroureteronephrosis up to the vesico-ureteric junction. A huge hetero-echoic pedunculated mass 10 cm in size, with smooth surface and well-defined margin was seen in the bladder, occupying the entire bladder surface [Figure - 1].

Contrast enhanced CT scan of the abdomen revealed normal liver, pancreas and adrenals. Both kidneys showed mild hydroureteronephrosis [Figure - 2] with a 10 mm simple cyst in the interpolar region of the right kidney. There was a large heterodense mass in the bladder, occupying most of the bladder [Figure - 3]. There were multiple enlarged lymph nodes involving the para-iliac, right external iliac, left internal iliac and left inguinal regions, each 7-8 mm in size, in transverse diameter.

Pathological discussion

On microscopic examination, the entire tumour was infiltrated by nests of polygonal cells with oval vesicular to hyper chromatic nuclei and eosinophilic to clear cytoplasm [Figure - 4]. Cystically dilated cells were also present. The intervening stroma consisted of spindle cells with fusiform nuclei, compressing the cell nests in some areas, forming broad, polypoid projections [Figure - 5]. There were areas of necrosis with acute inflammatory reaction. The metaplastic stromal cells showed no increase in mitotic activity.

The NV-TCC was first described as a malignant tumor by Talbert and Young in 1989.This lesion has a characteristic deceptive appearance. A confluence of small nests or abortive tubules of urothelial cells infiltrating the lamina propria and/or muscularis propria is characteristic of this condition.[2] Though the neoplastic cells tend to have innocuous features, in every case, there are foci of cytologically malignant cells, especially in the deeper layers of the tumor. They contain urothelial cells with a mild pleomorphism, slightly increased nuclear/ cytoplasmic ratio and occasionally prominent nucleoli. The differential diagnosis includes prominent Von-brunn's nests, cystitis cystica, cystitis glandularis, Nephrogenic metaplasia, Inverted papilloma and paraganglioma.[3] Multiple biological markers have also been evaluated in conventional urothelial carcinomas in an attempt to understand better the molecular events that lead to disease progression and to study the correlation with the tumor grade and behavior. Some of these markers include P 21, P27, P53, EGF-r, bcl-2 and MIB. In general, loss or absence of immunoreactivity for cyclin-dependent kinases p21 and p27 has been associated with poor prognosis in conventional TCC.[4]

The aggressive behavior of these nested variants underlines the importance of distinguishing them from benign proliferative lesions. Cytologic atypia is not a very good parameter because the mild atypia seen in the NV-TCC can be very much deceptive, especially at low and medium power magnifications. Though the obvious invasion of the muscularis propria excludes the possibility of a benign lesion, the absence of invasion leads the pathologist onto a diagnostic dilemma.

   Discussion Top

The NV-TCC is an uncommon neoplasm in the urinary bladder. It is usually a disease of the middle-aged and elderly. The most common and one of the earliest symptoms in these patients is gross macroscopic hematuria, which occurs in 75-90% of the patients. Other symptoms may be related to the size of the mass and irritation of the bladder mucosa, including retention of urine, interrupted stream, dysuria, frequency and nocturia.[5]

The NV-TCC is characterized by a focus of nests of transitional epithelial cells that infiltrate the lamina propria with no apparent involvement of the bladder mucosa.[6] These tumor cells are organized in nested structures. Many of the tumor cells are only slightly atypical but a careful examination revealed that at least some significantly anaplastic cells are identifiable in each case, the degree of anaplasia tending to parallel the depth of invasion. The features that identify this lesion as malignant are the tendency for increasing cellular anaplasia in the deeper portions of the lesion, its infiltrative nature and the presence of muscle invasion.[7] Despite the mild or minimal cytological atypia, these neoplasms are occasionally associated with an aggressive clinical course and even death.[8]

Sue Min et al[9] reported a rare presentation of NV-TCC in a patient with bilateral hydronephrosis with tumor obliteration of one ureter with extensive liver and bony metastases who eventually died 12 months after diagnosis. Though anecdotal reports of adjunctive chemotherapy with Gemcitabine and Carboplatin are being reported, no randomized studies are available on the effects of adjunctive chemotherapy in these patients with NV-TCC, post cystectomy.[9] Holmang and Johansson reported no survival advantage with adjunctive radiotherapy in their series of seven patients with the T stage in cystectomy specimens ranging from T 1 to T 4B.[10]

The NV-TCC is aggressive, invasive, with a very well-differentiated histology, which is difficult to understand. However, it is suggested that the unusual histology may be due to the peculiarities of the host response mechanisms to carcinogenic stimulus such that the host is able to channel differentiation, but cannot control invasion.[10]

Moreover, as NV-TCC can easily be confused with the above-mentioned benign lesions, it is very important for the pathologist to consider NV-TCC in the differential diagnosis of the lesions that show nested type of growth pattern in lesions of the urinary bladder. It is also important for the treating physician to adopt an aggressive approach towards the management of these lesions.

The optimal treatment for the NV-TCC is yet to be determined. This may be because of the rarity of the tumor, very small number of long-term survivors and the absence of any randomized studies. The aggressive invasive growth and early metastases are the factors that favor radical cystectomy with adjunctive systemic chemotherapy. However, a consensus is yet to be arrived at.

   References Top

1.Dundar E, Acikalin MF, Can C. The nested variant of urothelial carcinoma: An aggressive tumor closely simulating benign lesions. Pathol Oncol Res 2006;12:105-7.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Talbert ML, Young RH. Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases. Am J Surg Pathol 1989;13:374-81.  Back to cited text no. 2    
3.Drew PA, Furman J, Civantos F, Murphy WM. The nested variant of transitional cell carcinoma: An aggressive neoplasm with innocuous histology. Mod Pathol 1996;9:989-94.  Back to cited text no. 3  [PUBMED]  
4.Lin O, Cardillo M, Dalbagni G, Linkov I, Hutchinson B, Reuter VE. Nested variant of urothelial carcinoma: A clinicopathologic and immunohistochemical study of 12 cases. Mod Pathol 2003;16:1289-98.  Back to cited text no. 4  [PUBMED]  
5.Ozdemir BH, Ozdemir G, Sertcelik A. The nested variant of the transitional cell bladder carcinoma: A case report and review of the literature. Int Urol Nephrol 2000;32:257-8.  Back to cited text no. 5    
6.Tatsura H, Ogawa K, Sakata T, Okamura T. A nested variant of transitional cell carcinoma of the urinary bladder: A case report. Jpn J Clin Oncol 2001;31:287-9.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Murphy WM, Deana DG. The nested variant of transitional cell carcinoma: A neoplasm resembling proliferation of Brunn's nests. Mod Pathol 1992;5:240-3.  Back to cited text no. 7  [PUBMED]  
8.Mai KT, Elmontaser G, Perkins DG, Yazdi HM, Stinson WA, Thijssen A. Histopathological and immunohistochemical study of papillary urothelial neoplasms of low malignant potential and grade associated with extensive invasive low-grade urothelial carcinoma. BJU Int 2004;94:544-7.  Back to cited text no. 8    
9.Ooi SM, Vivian J, Sinniah R, Troon S. Nested variant of urothelial carcinoma: A rare presentation. Urology 2006;67:845.e3-5.  Back to cited text no. 9    
10.Holmang S, Johansson SL. The nested variant of transitional cell carcinoma: A rare neoplasm with poor prognosis. Scand J Urol Nephrol 2001;35:102-5.  Back to cited text no. 10    


  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]


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