Abstract
Urinary stones are known predisposing factors for upper urinary tract carcinoma (UUTC) which are commonly detected at advanced stage with poor outcome because of rarity and lack of specific criteria for early detection. The main aim was to evaluate the impact of age, gender andstone characteristics on risk of developing UUTC in patients with chronic nephrolithiasis. We also discuss the role of aberrant angiogenesis (AA) and immunohistochemical expression of p53, p16INK4a, CK20 and Ki-67 in diagnosis of pelvicalyceal neoplastic (NL) and pre-neoplastic lesions (PNL) in these patients. Retrospective analysis of pelvicalyceal urothelial lesions from 88 nephrectomy specimens were carried out in a tertiary care centre from June 2012 to December 2014. Immunohistochemistry (IHC) was performed on 37 selected cases. Computed image analysis was performed to analyse aberrant angiogenesis. All UUTC (5.7%) and metaplastic lesions were found to be associated with stones. Some 60% were pure squamous cell carcinoma and 40% were transitional cell carcinoma. Odd ratios for developing NL and PNL lesions in presence of renal stone, impacted stones, multiple and large stag horn stones were 9.39 (95% CI 1.15-76.39, p value 0.05), 6.28 (95% CI 1.59-24.85, p value 0.000) and 7.4 (95% CI, 2.29-23.94, p value 0.001) respectively. When patient age was ≥ 55, the odds ratio for developing NL was 3.43 (95% CI 1.19-9.88, p value 0.019). IHC analysis showed that mean Ki-67 indices were 3.15 ± 3.63 % for non-neoplastic lesions, 10.0±9.45 % for PNL and 28.0± 18.4% for NL. Sensitivity and specificity of CK20, p53, p16INK4a, AA were 76% and 95.9%; 100% and 27.5%; 100% and 26.5%; 92.3 % and 78.8% respectively. Age ≥55 years, large stag horn stones, multiple stones and impacted stones are found to be associated with increased risk of NL and PNL in UUT. For flat lesions, a panel of markers, Ki 67 index >10 and presence of aberrant angiogenesis were more useful than individual markers.
Highlights
Neglected renal stones are known predisposing factors for development of upper urinary tract carcinoma (UUTC)
We discuss the role of aberrant angiogenesis (AA) and immunohistochemical expression of p53, p16INK4a, CK20 and Ki-67 in diagnosis of pelvicalyceal neoplastic (NL) and pre-neoplastic lesions (PNL) in these patients
We found that the risk of NL was increased dysplasia, 4 (4.5%) carcinoma in situ, 4 (4.5%), low grade when age of patient was ≥ 55 years. (chi square p value papillary lesions, 2 (2.3%) high grade papillary urothelial 0.019. odd ratio 3.429 with 95% CI 1.190-9.877)
Summary
Neglected renal stones are known predisposing factors for development of upper urinary tract carcinoma (UUTC). Pre-neoplastic lesions associated with stones have been described by very few studies (Beyer-Boon et al, 1978, Deniz et al, 2010; Hong et al, 2014; Zhou et al, 2014) These lesions are commonly missed because of nonspecific clinical presentation and conventional radiological findings due to presence of renal stones and often detected at advanced stage with poor outcome (Raghavendran et al, 2003; Hong et al, 2014; Rheaume-Lanoie et al, 2014). Odd ratios for developing NL and PNL lesions in presence of renal stone, impacted stones, multiple and large stag horn stones were 9.39 (95% CI 1.15-76.39, p value 0.05), 6.28 (95% CI 1.59-24.85, p value 0.000) and 7.4 (95% CI, 2.29-23.94, p value 0.001) respectively. A panel of markers, Ki 67 index >10 and presence of aberrant angiogenesis were more useful than individual markers
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