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CORRESPONDENCE
Year : 2019  |  Volume : 15  |  Issue : 8  |  Page : 159-162

Staging a great escape -Incidentally detected renal urothelial carcinoma with extensive squamous metaplasia presenting as pyonephrosis


1 Department of Pathology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
2 Department of Surgery, Maulana Azad Medical College, New Delhi, India

Date of Web Publication22-Mar-2019

Correspondence Address:
Dr. Ravindra Kumar Saran
Department of Pathology, Academic Block, Room Number 333, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_628_17

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 > Abstract 


Incidentally, detected upper urinary tract urothelial carcinoma is a rare entity. We report the case of a 70-year-old female patient who presented with flank pain, pyuria, fever, and a unilateral nonfunctioning kidney with nephrolithiasis and pyonephrosis on pyelography. Routine imaging failed to identify a mass lesion. In an Indian setting, the clinical differential of tuberculosis was considered likely. A nephrectomy was performed in view of the poor perfusion and functional status of the right kidney. Histopathological examination of the kidney showed a tumor of urothelial origin arising at the renal pelvis displaying extensive squamous metaplasia. Such a near total metaplastic change is rare and has hitherto been undescribed in the renal pelvis. Activation of pleuripotent urothelial stem cells in the setting of chronic irritation and inflammation may be the pathogenetic process behind such an occurrence.

Keywords: Carcinoma, pyonephrosis, squamous, transitional cell


How to cite this article:
Gaur K, Gupta L, Saran RK, Ghuliani D. Staging a great escape -Incidentally detected renal urothelial carcinoma with extensive squamous metaplasia presenting as pyonephrosis. J Can Res Ther 2019;15, Suppl S1:159-62

How to cite this URL:
Gaur K, Gupta L, Saran RK, Ghuliani D. Staging a great escape -Incidentally detected renal urothelial carcinoma with extensive squamous metaplasia presenting as pyonephrosis. J Can Res Ther [serial online] 2019 [cited 2019 Nov 22];15:159-62. Available from: http://www.cancerjournal.net/text.asp?2019/15/8/159/244227




 > Introduction Top


Incidentally, detected urothelial carcinoma (UC) of the renal pelvis is a rare entity.[1] Upper tract UC is uncommon, comprising approximately 7% of all renal tumors.[2] Although UC of renal pelvis may show squamous differentiation (SD) in about 40% of cases,[3] extensive replacement of the urothelial component by SD, to the best of our knowledge, has previously been described only once and that too in in the context of urinary bladder UC.[4] Such extensive metaplasia has previously not been documented at the renal pelvis. In addition, the fact that this histological occurrence was detected in the absence of radiological evidence of a mass lesion in the clinical setting of pyonephrosis makes this noteworthy from a clinical and diagnostic standpoint.


 > Case Report Top


A 70-year-old female presented with a right flank lump associated with pain and weight loss for 6 months. There was no history of hematuria, trauma, or lumps elsewhere. Clinically, a smooth and firm lump was palpable in the right flank extending to the umbilicus, moving with respiration. Investigations revealed reduced hemoglobin (11.2 g/dl) and elevated total leukocyte count (TLC-13600 cells/cumm). Urine microscopy showed numerous pus cells and occasional red blood cells. Urine culture failed to isolate any growth. Other laboratory parameters including serum creatinine, blood urea, and sugar were normal. X-ray showed an enlarged right renal shadow with multiple well-defined radio-opaque calculi [Figure 1]a. Abdominal ultrasonogram (USG) showed an enlarged right kidney with internal echoes measuring 6 cm × 4.5 cm in the renal pelvis and gross hydronephrosis [Figure 1]b. Intravenous pyelogram showed features of a nonexcretory, hydronephrotic right kidney with multiple renal calculi [Figure 1]c.99m Tc-DTPA scan revealed poor perfusion and tracer activity in the right renal fossa and an unremarkable left kidney [Figure 1]d. Glomerular filtration rates in the right and left kidney were 3.81 and 64.08 ml/min, respectively. A clinical impression of the right pyonephrotic nonfunctioning kidney was made following which the patient was taken up for right simple nephrectomy through subcostal incision.
Figure 1: (a) X-ray kidney, ureter, and bladder showing multiple calculi; (b) Abdominal ultrasound showing echogenicity in the right kidney suggestive of hydronephrosis; (c) intravenous pyelogram at 5 min showing non excretory right kidney with multiple calculi; and (d) 99mTcDTPA scan showing poor perfusion and tracer activity in the right renal fossa. Inset shows time-activity curves showing markedly diminished right renal function

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Peroperatively, the right kidney appeared pyonephrotic with multiple calculi and dense perinephric adhesions. A necrotic perinephric lymph node was identified at the upper pole. The postoperative period was uneventful.

Histopathology

Grossly, a specimen of right kidney measuring 13 cm × 8 cm × 4 cm was received. On sectioning, the pelvicalyceal system showed purulent material and multiple large multifaceted stones. An infiltrating whitish-yellow tumor with ill-defined margins was noted at the upper pole extending to the renal pelvis [Figure 2].
Figure 2: Gross specimen of right kidney showing dilated pelvicalyceal system filled with multiple large multifaceted stones and an infiltrating ill-defined whitish-yellow tumor at the pelvis extending into upper pole with necrotic areas

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Microscopically, the tumor had an invasive growth pattern largely comprised nests of malignant squamous looking cells with extensive necrosis and evidence of keratin production [Figure 3]a. Focal areas showed an organoid nesting pattern [Figure 3]b. The tumor showed capsular breach, invaded the perirenal fascia sparing the renal vessels. Tumor nests showed CK7 and 20 immunopositivity and focal CK5/6 positivity [Figure 4]a,[Figure 4]b,[Figure 4]c. Sections from the grossly yellow looking areas showed cords of small polygonal tumor cells [Figure 3]c immunonegative for CK5/6, CK7, CK20, vimentin, epithelial membrane antigen, CD 10, synaptophysin, chromogranin, HMB-45, and WT1. Multiple sections were also taken from the renal pelvis and ureter. Sections of the pelvis showed full-thickness dysplasia and squamous metaplasia of the lining urothelium [Figure 3]d and [Figure 3]e. The ureter showed lamina invasion by tumor nests [Figure 3]f. The resected perinephric lymph node showed large areas of necrosis and malignant squamous cells with keratin pearls and focal CK5/6 immunopositivity of tumor cells [Figure 4]d. The perinephric fat was free of tumor. A diagnosis of UC with extensive SD and nodal metastasis was made. Subsequent work up of the patient failed to reveal any other focus of malignancy. The patient is currently on regular follow-up and is free of any symptoms.
Figure 3: (a) H and E (×100) Infiltrative tumor showing squamous differentiation with keratin pearls; and (b) a focal organoid pattern; (c) H and E (×100) showing cords of tumor cells showing small round morphology; (d and e) H and E (×100 and × 200) showing dysplasia and squamous metaplasia of transitional lining at pelvis; (f) H and E (×20) showing lamina invasion by papillary urothelial carcinoma in ureter

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Figure 4: (a and b) CK7 and CK20 (×200) positivity in tumor cells; (c) CK5/6 (200x) patchy positive tumor cells; and (d) CK5/6 (×100) positive tumor deposits in lymph node

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 > Discussion Top


Incidental UC of the upper urinary tract is uncommon. In a study on 500 percutaneous nephrolithotomies, Katz et al.[5] found three patients in whom the diagnosis of UC escaped clinical or radiological suspicion. In the present case, pyuria, the absence of a mass lesion on routine imaging and a pyonephrotic kidney with a peroperative necrotic lymph node made tuberculosis an important clinical possibility, especially in an Indian context.

How this tumor escaped conventional methods of detection is noteworthy. The cases of UC encountered by Katz et al.[5] showed similar “escapist” tendencies. Our patient presented clinically with flank pain and weakness sans hematuria. UC of the upper urinary tract commonly manifests as hematuria, seen in 70%–80% of cases.[6] The absence of a mass lesion on routine imaging in such a setting inevitably delayed the diagnosis. On ultrasonography, UC may not disturb the renal contour[6] as seen here. The tumor on sonography may appear hyperechoic in relation to the normal renal parenchyma and may be obscured by the hyperechoicity of perirenal sinus fat.[7] USG findings may also mimic tuberculosis thus compounding the problem.[8] Retrospectively, we acknowledge that preoperative computed tomography (CT) could have nailed the diagnosis earlier; however, CT itself is not full proof. Some studies[9] even suggest that CT may be a better modality for defining the anatomical extent of a lesion rather than pinpointing the exact tumor type.

Although the role of cytology in detection of upper urinary tract UC is still a subject of investigation, recent work by Tai et al.[10] has clearly demonstrated that reliance on a single diagnostic tool may not be prudent. Three days random urine cytology may serve as a useful adjunct minimizing potential “escapes.” Similarly, upper tract wash cytology has been demonstrated to have 71.4% and 91.9% sensitivity and specificity for detecting high-grade UC.[11] In a resource constrained scenario, cytology may well be a useful modality.

Histopathological sections revealed a tumor morphologically appearing squamoid. Primary intraparenchymal squamous cell carcinoma (SCC) of the kidney is, however, rare.[12] Previous reports have emphasized the need to rule out primary UC with SD and metastatic SCC before diagnosing primary SCC.[12] Subsequent sections and deeper cuts of the existing sections of the renal pelvis revealed the UC component which was masked due to the prominent SD immunohistochemical positivity of CK 7 and 20 strengthened the diagnosis.

Various theories have been put forward for the squamous metaplasia in UC including transdifferentiation, redifferentiation, pleuripotent stem cells, and expansion of selected clones.[13] In this case, we suggest that in the milieu of chronic inflammation, activation of pleuripotent urothelial stem cells may have occurred; a fact supported by the presence of urothelial, squamoid, and undifferentiated components within the tumor.

Divergent differentiation is seen in tumors afflicting both the bladder and renal pelvis.[14] SD in UC is a harbinger of grave prognosis, some reports suggesting it to imply a resistance to radiotherapeutic regimens.[15] The extent of SD in a UC is highly variable, very few cases describe near total replacement of the native urothelial component by SD[4] as seen herein. Meticulous and extensive sampling of the renal pelvis is, therefore, essential. Failure to do so could easily result in incorrect histological typing with subsequent bearing on surgical management.

To conclude, in the absence of hematuria, two Cs – CT and cytology must be carried out for the elderly patient with a nonfunctioning kidney. Further studies would be required to validate such an approach.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Jain KA. Transitional cell carcinoma of the renal pelvis presenting as pyonephrosis. J Ultrasound Med 2007;26:971-5.  Back to cited text no. 1
    
2.
Kim WJ, Chung JI, Hong JH, Kim CS, Jung SI, Yoon DK. Epidemiological study for urologic cancer in Korea (1998-2002). Korean J Urol 2004;45:1081-8.  Back to cited text no. 2
    
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Nigwekar P, Amin MB. The many faces of urothelial carcinoma: An update with an emphasis on recently described variants. Adv Anat Pathol 2008;15:218-33.  Back to cited text no. 3
    
4.
Sakamoto N, Tsuneyoshi M, Enjoji M. Urinary bladder carcinoma with a neoplastic squamous component: A mapping study of 31 cases. Histopathology 1992;21:135-41.  Back to cited text no. 4
    
5.
Katz R, Gofrit ON, Golijanin D, Landau EH, Shapiro A, Pode D, et al. Urothelial cancer of the renal pelvis in percutaneous nephrolithotomy patients. Urol Int 2005;75:17-20.  Back to cited text no. 5
    
6.
Cowan NC. CT urography for hematuria. Nat Rev Urol 2012;9:218-26.  Back to cited text no. 6
    
7.
Prando A, Prando P, Prando D. Urothelial cancer of the renal pelvicaliceal system: Unusual imaging manifestations. Radiographics 2010;30:1553-66.  Back to cited text no. 7
    
8.
López-Beltrán A, Martín J, García J, Toro M. Squamous and glandular differentiation in urothelial bladder carcinomas. Histopathology, histochemistry and immunohistochemical expression of carcinoembryonic antigen. Histol Histopathol 1988;3:63-8.  Back to cited text no. 8
    
9.
Wong-You-Cheong JJ, Wagner BJ, Davis CJ Jr. Transitional cell carcinoma of the urinary tract: Radiologic-pathologic correlation. Radiographics 1998;18:123-42.  Back to cited text no. 9
    
10.
Tai Y, Chiang I, Huang CH, Tai H, Pu Y. Effectiveness of different diagnostic tools for upper urinary tract urothelial carcinoma. Urol Sci 2015;26:57-60.  Back to cited text no. 10
    
11.
Huiying HE, Zhou M, Magi-Galluzzi C, Chen L. The diagnostic utility of urinary cytology in detecting upper tract urothelial carcinoma. Am J Clin Pathol 2012;138 Suppl 1:A029.  Back to cited text no. 11
    
12.
Diwan AK, Kabre RS. Primary squamous cell carcinoma of kidney: A rare case report. Int J Med Sci Res Pract 2015;2:49-53.  Back to cited text no. 12
    
13.
Wu XR, Kong XP, Pellicer A, Kreibich G, Sun TT. Uroplakins in urothelial biology, function, and disease. Kidney Int 2009;75:1153-65.  Back to cited text no. 13
    
14.
Perez-Montiel D, Wakely PE, Hes O, Michal M, Suster S. High-grade urothelial carcinoma of the renal pelvis: Clinicopathologic study of 108 cases with emphasis on unusual morphologic variants. Mod Pathol 2006;19:494-503.  Back to cited text no. 14
    
15.
Martin JE, Jenkins BJ, Zuk RJ, Blandy JP, Baithun SI. Clinical importance of squamous metaplasia in invasive transitional cell carcinoma of the bladder. J Clin Pathol 1989;42:250-3.  Back to cited text no. 15
    


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



 

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