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LETTER TO EDITOR  
Year : 2011  |  Volume : 54  |  Issue : 3  |  Page : 651-652
Urothelial carcinoma with multiple patterns of divergent differentiation featuring small cell, clear cell, papillary glandular and squamous cell morphology


Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India

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Date of Web Publication20-Sep-2011
 

How to cite this article:
Jain D, Dhawan S, Chopra P. Urothelial carcinoma with multiple patterns of divergent differentiation featuring small cell, clear cell, papillary glandular and squamous cell morphology. Indian J Pathol Microbiol 2011;54:651-2

How to cite this URL:
Jain D, Dhawan S, Chopra P. Urothelial carcinoma with multiple patterns of divergent differentiation featuring small cell, clear cell, papillary glandular and squamous cell morphology. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Nov 23];54:651-2. Available from: https://www.ijpmonline.org/text.asp?2011/54/3/651/85136


Sir,

Urothelial carcinoma (UC) accounts for nearly 90% of urinary bladder (UB) tumors. It is well known for its divergent morphology, including the most common squamous and glandular features. [1] A variety of histological variants of UC have been recently recognized. The clinical outcome and treatment protocol of some variants differ from those of typical UC. [2] It is essential for clinicians and pathologists to be aware of the morphological variants of urothelial cancer because of their differences in prognosis.

A 46-year-old male presented with hematuria of 3 months duration, which was painless, intermittent and mild-to-severe in intensity. The patient was a known diabetic and hypertensive with history of renal stones. Contrast-enhanced computerized tomography of the kidney and UB reveal evidence of mass lesion in relation to the UB particularly along the posterior and right lateral wall involving the distal right ureter, bilateral ureterovesical junctions with extravesical spread. Moderate degree of hydronephrosis was present. Multiple retroperitoneal lymph nodes and multiple space occupying lesions in the liver and nodules in the lungs, possibly metastatic in nature were identified. Cystoscopy revealed an extensive broad-based tumor involving the trigone and extending laterally on both sides obscuring bilateral ureteric orifices. Transurethral resection of bladder tumor was done. Microscopically, high-grade UC was seen with small cell [Figure 1]a and b, glandular [Figure 1]c, squamous [Figure 1]d and clear cell [Figure 1]e features. Squamous, glandular and small cell components encompassed approximately 20% of the tumor whereas clear cell phenotype represented around 5% of the tumor. Immunohistochemically, the cancer cells were positive for cytokeratin and epithelial membrane antigen. Small cells were positive for synaptophysin [Figure 1]f and chromogranin. The patient received no radiosurgical therapies because of the advanced stage of the disease with multiple metastases to the liver and lung.
Figure 1: (a) Photomicrograph showing papillary urothelial carcinoma with nuclear pleomorphism and increase mitotic activity, H and E, ×100, (b) muscle invasive small cell component shows nuclear hyperchromasia, H and E, ×200, (c) papillary fronds of glandular component lined by pleomorphic columnar cells, H and E, ×200, (d) squamous differentiation is evident with synctitial pattern and abundant eosinophilic cytoplasm, H and E, ×400, (e) clear cytoplasm is seen focally, H and E, ×400, (f) immunostain for synaptophysin shows immunoreactivity in small cell component

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A number of histologic variants of UC have been recognized to date. The most important of these are the histological phenotypes that are closely associated with clinical prognosis or outcome independent of nuclear grade. [3] Mixed urothelial tumors are described as two or more variant histological patterns in addition to conventional UC. [3] Morphologically, small cell carcinoma is identical to the undifferentiated small- cell carcinoma of the lung, but is more frequently admixed, in approximately 40-50% of the cases, with an epithelial component of UC. Up to two-thirds of cases of UC have foci of clear-cell change resulting from abundant glycogen. Cytokeratin 7 stain denotes urothelial origin and resolves other clear cell carcinomas. [3] Approximately 10% of UCs contain foci of glandular and up to 60% of tumors exhibit squamous differentiation. [2] Although the prognostic significance of squamous or glandular differentiation is unclear, some studies have suggested a higher rate of metastases in mixed tumors showing two or more variant histological patterns in addition to conventional urothelial carcinoma. [4]

Divergent morphology is a common histologic feature of high-grade urothelial carcinomas. Pathologists and urologists should be aware of these infrequent variants, which are associated with aggressive clinical behavior.

 
   References Top

1.Eble JN, Sauter G, Epstein JI, Sesterhenn IA. World Health Organization Classification of Tumours. Pathology and Genetics of Tumors of the Urinary System and Male Genital Organs. Lyon: IARC press; 2004.  Back to cited text no. 1
    
2.Amin MB. Histological variants of urothelial carcinoma: Diagnostic, therapeutic and prognostic implications. Mod Pathol 2009;22: S96-S118.  Back to cited text no. 2
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3.Lopez-Beltran A, Requena MJ, Cheng L, Montironi R. Pathological variants of invasive bladder cancer according to their suggested clinical significance. BJU Int 2008;101:275-81.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Domanowska E, Jozwicki W, Domaniewski J, Golda R, Skok Z, Wis´niewska H, et al. Muscle invasive urothelial cell carcinoma of the human bladder: Multidirectional differentiation and ability to metastasize. Hum Pathol 2007;38:741-6.  Back to cited text no. 4
    

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Correspondence Address:
Deepali Jain
Department of Pathology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi - 110 060
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.85136

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