Angela B. Smith, MD
Raj S. Pruthi, MD, FACS
BASICS
DESCRIPTION
• Squamous-cell carcinoma (SCC) of the renal pelvis and ureter is a rare but aggressive tumor characterized by nests of squamous cells with hyperchromatic nuclei and prominent keratin production.
• Most common non-urothelial tumor of the upper urinary tract.
EPIDEMIOLOGY
Incidence
• 0.5–0.8% of all malignant renal tumors (1)[C]
• 6–15% of all upper tract urothelial cancers (4)[C]
• Mean age 61 yr
• Equal incidence male:female (although some series suggest male predominance) (2,3)[C]
• 6× more likely to occur in the renal pelvis than in the ureter
Prevalence
• Prevalence unknown due to rarity of tumor
– Rare tumor, with case reports in literature
RISK FACTORS
• Chronic inflammation (4)[C]
• Chronic infections associated with (4)[C]
– Urinary stones
– Obstruction
• Cyclophosphamide (alkylating agent) shown to increase risk of upper tract SCC
Genetics
• No specific genetic patterns identified
• Possible that DNA ploidy pattern correlates with grade and stage but does not aid prognosis
– Not definitive; requires further study (3)[C]
PATHOPHYSIOLOGY
• SCC of the renal pelvis and ureter has been shown to be associated with chronic infection and inflammation
– Presumed that chronic irritation of urothelium leads to squamous metaplasia and subsequent SCC
ASSOCIATED CONDITIONS
• Chronic infections: (4)[C]
– Genitourinary tuberculosis
– Struvite stones
– Chronic pyelonephritis or pyonephrosis
– Parasitic infection
• Chronic inflammation: (4)[C]
– Analgesic abuse
– Prior percutaneous nephrolithotomy
• Horseshoe kidney (3× risk due to stones/infection) (4)[C]
• Renal or ureteral calculi (4)[C]
– Present in up to 50% of cases
• Bladder cancer history uncommon (3)[C]
– 5% preceding diagnosis
– 2% with concomitant bladder cancer
GENERAL PREVENTION
As a rare condition, little evidence exists for prevention of this condition
DIAGNOSIS
HISTORY
• History of chronic renal infections or stones
• Vague abdominal or flank pain
• Gross hematuria
• Local symptoms more common than those with TCC urothelial carcinoma (4)[C]
• Nonspecific symptoms:
– Anorexia
– Lethargy
– Weight loss
PHYSICAL EXAM
• Often no signs on physical exam
• Flank or abdominal mass may be present with advanced disease
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis:
– Hematuria
– Pyuria
• Serum chemistries (3)[C]
– Serum creatinine may be elevated due to tumor infiltration, obstruction, chronic infection, or scarring
– Paraneoplastic syndrome which may resolve following resection includes:
Hypercalcemia
Leukocytosis
Thrombocytosis
Imaging
• Diagnosis suggested (but not definitive) with radiologic imaging
• Excretory imaging useful (including intravenous pyelogram, CT urogram) and may demonstrate:
– Filling defect
– Solid mass w/ or w/o calcifications
– Hydronephrosis
• Once pathology confirmed, CT or MRI/MRA necessary for surgical planning
– Vascular anatomy
– Presence of metastases
– Evaluation of contralateral renal unit
– Size and extent of tumor
Diagnostic Procedures/Surgery
• Cystoscopy to evaluate for lower tract urothelial cancer, selective ureteral cytology
• Retrograde ureteropyelogram and ureteroscopy/pyeloscopy with biopsy essential
– Often with sessile appearance
– May have calcifications
• Definitive diagnosis confirmed following nephroureterectomy (see TREATMENT)
Pathologic Findings
• Most moderately or poorly differentiated
• Gross (1)[C]
– Infiltrating at time of diagnosis
– Sessile tumor on endoscopy
– Usually large, necrotic, ulcerated
• Histology (5)[C]
– Sheets of cells with deeply eosinophilic cytoplasm
– Large nuclei with prominent nucleoli
– Focal keratin pearl formation
Keratin pearls and intercellular bridges may not be apparent in advanced cases
DIFFERENTIAL DIAGNOSIS
• Primary renal neoplasms
– Renal cell carcinoma
– Urothelial cancer (TCC) of upper tract
– Wilms tumor
• Secondary renal neoplasms
– Lymphoma/leukemia
– Metastasis to kidney (breast, lung, and others)
• Benign renal masses
– Xanthogranulomatous pyelonephritis
– Rare form of chronic pyelonephritis
– Angiomyolipoma
TREATMENT
GENERAL MEASURES
Surgery (nephroureterectomy) is mainstay of treatment (3)[C]
MEDICATION
First Line
Medical therapy not effective although some patients require broad-spectrum antibiotics in the setting of concurrent infection
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Referent standard treatment is surgical excision (radical nephroureterectomy with excision of bladder cuff) (3)[C]
• Role of retroperitoneal lymph node dissection controversial
• For those patients with infection, pre- and post-operative antibiotics may be required
ADDITIONAL TREATMENT
Radiation Therapy
Occasionally used for adjuvant treatment following surgery; however shown to have little benefit (1)[C]
Additional Therapies
Adjuvant platinum-based chemotherapy appears to have limited benefit (3)[C]
Complementary & Alternative Therapies
No complementary therapies have shown benefit
ONGOING CARE
PROGNOSIS
• Generally poor if found at advanced stage
– Median survival of 7–14 mo postoperatively (2 – 4)[C]
– Median 5-yr survival 7.7% (3)[C]
• Tumor stage at diagnosis most important for prognosis (3)[C]
• Grade has been found to add little value (3)[C]
COMPLICATIONS
• Renal insufficiency or failure
• Metastatic disease (3)[C]
– Regional lymph nodes
– Lungs
– Liver
– Bone
FOLLOW-UP
Patient Monitoring
• Limited data for patient monitoring
• Similar to TCC of upper tract
– Urine cytology and cystoscopy every 3–4 mo for first 2 yr
– Value of cystoscopy questionable due to low number of concurrent bladder cancers
• Metastatic workup every 6–12 mo, depending on stage
– Chest imaging
– CT abdomen/pelvis
• Monitor renal function periodically
Patient Resources
Urology Care Foundation. http://www.urologyhealth.org/urology/index.cfm?article=39
REFERENCES
1. Kayalselcuk F, Bal N, Guvel S, et al. Carcinosarcoma and squamous cell carcinoma of the renal pelvis associated with nephrolithiasis: A case report of each tumor type. Pathol Res Pract. 2003;199:489–492.
2. Nativ O, Reiman HM, Lieber MM, et al. Treatment of primary squamous cell carcinoma of the upper urinary tract. Cancer. 1991;68:2575–2578.
3. Holmäng S, Lele SM, Johansson SL. Squamous cell carcinoma of the renal pelvis and ureter: Incidence, symptoms, treatment and outcome. J Urol. 2007;178(1):51–56.
4. Busby JE, Brown GA, Tamboli P, et al. Upper urinary tract tumors with nontransitional histology: a single-center experience. Urology. 2006;67(3):518–523.
5. Perez-Montiel D, Wakely PE, Hes O, et al. High-grade urothelial carcinoma of the renal pelvis: Clinicopathologic study of 108 cases with emphasis on unusual morphologic variants. Mod Pathol. 2006;19(4):494–503.
ADDITIONAL READING
• Xylinas E, Rink M, Margulis V, et al. Histologic variants of upper tract urothelial carcinoma do not affect response to adjuvant chemotherapy after radical nephroureterectomy. Eur Urol. 2012;62(1):e25–e26.
• Rouprêt M, Babjuk M, Compérat E, et al. ; European Association of Urology. European guidelines on upper tract urothelial carcinomas: 2013 update. Eur Urol. 2013;63(6):1059–1071.
See Also (Topic, Algorithm, Media)
• Filling Defect, Upper Urinary Tract (Renal Pelvis and Ureter)
• Reference Tables: TNM: Renal Pelvis and Ureter Cancer
• Ureter and Renal Pelvic Tumors, General Considerations
• Ureter and Renal Pelvis, Squamous Cell Carcinoma Image 
• Ureter and Renal Pelvis, Urothelial Carcinoma
CODES
ICD9
• 189.1 Malignant neoplasm of renal pelvis
• 189.2 Malignant neoplasm of ureter
ICD10
• C65.1 Malignant neoplasm of right renal pelvis
• C65.9 Malignant neoplasm of unspecified renal pelvis
• C66.9 Malignant neoplasm of unspecified ureter
CLINICAL/SURGICAL PEARLS
• SCC of upper tract is the most common non-urothelial cancer of the renal pelvis and ureter.
• A few symptoms manifest, but once hematuria and pain present, often advanced stage.
• Usually presents as advanced disease and has poor prognosis at this stage.
• Nephroureterectomy is standard of care with chemotherapy and radiation of limited benefit.