INTRODUCTION
The majority of malignant renal pelvic and ureteral tumors are of epithelial origin. Among these, ~90% are transitional cell carcinoma followed by squamous cell carcinoma (<10%).[1–3] Primary adenocarcinomas of the urothelium are rare, accounting for < 1% of all urothelial tumors.[4] Additionally, for adenocarcinoma to be located in the pelvis is uncommon and in the ureter is extremely rare. Adenocarcinoma of the upper urinary tract is usually subdivided into tubulovillous (71.5%), mucinous (21.5%), and papillary non-intestinal (7.0%).[5] Mucinous adenocarcinoma is presumed to be originating from intestinal metaplasia of the transitional epithelium.[6] Very few cases have been documented to confirm the above association.[6] It is also considered to be related to chronic irritation such as urolithiasis, infection, inflammation, and hydronephrosis.[7] Here, we report a case of mucinous adenocarcinoma of the renal pelvis and invasive adenocarcinoma of the ureter with intestinal metaplasia and dysplasia in the ureter—the whole spectrum, in the presence of a staghorn calculus.
CASE REPORT
This is a case of a 45-year-old female patient who presented in the outpatient department with pain and a lump in the abdomen for 2 months. Pelvic ultrasound revealed an enlarged right kidney with architectural distortion, gross parenchymal thinning, and multiple calculi within the renal pelvis, the largest measuring 3.8 cm in size. On plain and post-contrast computed tomography (CT) scan, the right kidney measured 23 × 10 cm and showed severe hydronephrosis with cortical thinning. An enhancing mass was also noted in the right proximal ureter over a length of approximately 2.8 cm with a maximum thickness of 1.2 cm, causing luminal narrowing. Enhancing masses were also noted within the renal pelvis. The kidney showed no excretion of contrast. Multiple calculi were noted in the right kidney, the largest measuring 4.9 × 1.8 cm in the renal pelvis. Radiological opinion was severe right-sided hydronephrosis with right renal calculi and enhancing masses in the right proximal ureter and renal pelvis, suggestive of neoplastic etiology. Cystoscopy revealed two small basal nodular areas over the interureteric region near the right ureteric orifice. Fulguration of these areas was performed. Right nephrectomy and right ureterectomy were performed with the removal of the cuff of the bladder.
On gross examination, the right kidney measured 21 × 14 × 10 cm with the ureter measuring 9 cm in length. The architecture of the entire kidney was distorted and it was replaced by multiple large cysts ranging in size from 0.5 to 8.5 cm in diameter. The cystic masses were filled with mucinous material surrounded by areas of exudate [Figure 1a and b]. A large staghorn calculus measuring 6 × 4 × 2 cm was present in the right pelviureteric junction where a few solid papillary areas were observed [Figure 1c]. A necrotic growth measuring 3 × 2 cm was noted in the right upper ureteric region, which was observed to extend into the ureter for about 3 cm but did not appear to reach up to the margin of excision of the ureter.
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Figure 1: (a) Image of a gross specimen of the kidney-external surface. (b) Image of a gross specimen of the kidney-cut section showing solidified mucin and papillary projections. (c) Image of the staghorn horn calculus found in the renal pelvis
Microscopic examination of the ureteric mass revealed acini and papillary projections lined by pseudostratified columnar epithelium showing malignant changes. Cells had a moderate amount of cytoplasm and hyperchromatic nucleus with prominent nucleoli [Figure 2a and b]. In some places, the glands were crowded back-to-back forming a cribriform pattern, whereas some were observed to lie in pools of mucin. Large areas of necrosis were also observed. The malignancy was observed to infiltrate the inner two-thirds of the wall of the ureteric muscular layer [Figure 3a]. Surrounding areas from the ureter revealed intestinal metaplasia with moderate-to-marked dysplasia in some places [Figure 3b-d]. Growth was observed to extend through the entire ureter and involve even the distal end. Sections from the solid papillary projections in the renal pelvis also revealed mucinous adenocarcinoma [Figure 2c and d] with similar intestinal metaplasia and dysplasia. However, sections from other solid and mucinous areas from the rest of the kidney revealed intestinal metaplasia, dysplasia, and pools of mucin. Mucin was also observed to infiltrate through the cyst wall, which revealed fibrocollagenous tissue with chronic inflammatory infiltrate comprising lymphocytes and foamy histiocytes. Some cysts also revealed areas of necrosis and acute inflammation. The surrounding kidney showed thyroidization of the tubules and chronic inflammation. A conclusion of mucinous adenocarcinoma of the right ureter and right renal pelvis with intestinal metaplasia and dysplasia with chronic pyelonephritis associated with staghorn calculus in the pelviureteric junction was made.
Figure 2: (a) Microphotograph of a histopathological section of the uterine growth showing malignant acini crowded back-to-back forming a cribriform pattern (10×). (b) Microphotograph of a histopathological section of the uterine growth showing malignant acini crowded back-to-back forming a cribriform pattern. Note the hyperchromatic nuclei with prominent nucleoli () (40×). (c), (d) Microphotograph of a histopathological section from the renal pelvis showing adenocarcinoma (with a cribriform pattern) with extracellular mucin (10×)
Figure 3: (a) Microphotograph of a histopathological section from the uterine wall showing infiltration by the adenocarcinoma (40×). (b) Microphotograph of a histopathological section from the ureter showing acini lined by the dysplastic pseudostratified epithelium (10×). (c) Microphotograph of a histopathological section from the ureter showing acini lined by dysplastic pseudostratified epithelium (40×). (d) Microphotograph of a histopathological section from the ureter showing intestinal metaplasia (10×)
DISCUSSION
The majority of the tumors of the renal pelvis and ureter have a distinct pathology. The most frequently observed tumor is urothelial carcinoma accounting for 90% of all tumors.[2] Primary adenocarcinoma of the upper urinary tract is rare and to date, <150 cases have been reported worldwide, of which the highest are from Asian countries such as Japan and India.[2,4] These patients are usually above 60 years of age and present with non-specific symptoms such as flank pain, abdominal mass, and hematuria.[2,4,5,7] Studies have also suggested that renal pelvic and ureter adenocarcinomas are often associated with chronic inflammation and subsequent chronic infection, hydronephrosis, and urinary calculi.[2] Chow et al. found significantly increased rates of renal pelvis and ureter cancer among patients admitted for upper urinary tract stones.[8] Our patient presented with pain and a lump in the abdomen and later revealed severe hydronephrosis with multiple calculi, especially a large stag horn calculus in the renal pelvis.
The radiological investigations required for making a diagnosis include ultrasonography, intravenous, and retrograde urography, CT, and if needed Doppler study and Diethylene triamine pentaacetic acid (DTPA) scan.[3] Preoperative diagnosis of this tumor is difficult, and the final diagnosis is certainly by postoperative histopathology. Similar to urothelial carcinoma, standard surgery is a radical nephroureterectomy with the removal of the bladder cuff.[7] It is important to remove the bladder cuff because of high rates of ureteral stump recurrence, reported to be 30–75%.[3] A similar surgical procedure was followed in our case though there was microscopic involvement of the distal end of the ureter. Although the role of adjuvant chemotherapy and radiotherapy is controversial, Chaudhary P et al.[3] suggested that adjuvant treatment in the form of radiation should be strongly considered in cases with close or positive margins to reduce the chances of locoregional recurrence. Histologically, it is further classified as tubulovillous, mucinous, and papillary non-intestinal types.[3,6] Mucinous adenocarcinoma usually occurs following glandular metaplasia of the urothelium, which may occur as a response to injury often progressing to dysplasia and adenocarcinoma.[2,3,7] Although many studies have suggested this evolution of the condition, a few studies have confirmed it. Raphael et al.[6] were the first to do so due to the presence of carcinoma in situ in the ureter. Our case further confirms this association as we observed the entire spectrum of the pathogenesis of the disease, ranging from intestinal metaplasia, dysplasia, and carcinoma in situ to invasive adenocarcinoma of the ureter and renal pelvis in the presence of a staghorn calculus. Xiong et al.[2] reported the first case of multifocal adenocarcinomas involving the renal system. This case is another rare instance where invasive adenocarcinoma of both the renal pelvis and ureter are observed involving the urothelium.
However, primary adenocarcinoma of the urological region requires differentiation from more common metastatic adenocarcinomas, including direct, lymphatic, and hematogenous spread. The principal primary organs to be considered include the prostate, colon, female genital tract, appendix, stomach, and breast.[2] In this case, the presence of carcinoma in situ and associated metaplasia and dysplasia favors the primary origin of the tumor. Besides metastasis, glandular differentiation in urothelial carcinoma must be ruled out before giving a diagnosis of primary adenocarcinoma.[9] These glandular features are composed of enteric-type glands with columnar epithelium and mucin production with typical urothelial carcinoma components, which were absent in our case. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) have been found to be positive in the immunohistochemical staining in some patients whose serum levels of CEA and CA 19-9 were apparently elevated simultaneously and decreased after the resection of the tumor.[3] CEA has thus been suggested to be used as a marker for prognosis and recurrence.[6]
CONCLUSION
In conclusion, primary adenocarcinoma of the renal pelvis and ureter are rare and very few cases with multifocal urothelial involvement have been reported. This is one such case that also confirms the probable etiology and pathophysiology.
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.
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