Objectives

To examine racial differences in the distribution of histological subtypes of renal cell carcinoma (RCC) and associations with established RCC risk factors by subtype.



Materials and Methods

Tumours from 1532 consecutive patients with RCC who underwent nephrectomy at Vanderbilt University Medical Center (1998–2012) were classified as clear-cell, papillary, chromophobe and other subtypes. In pairwise comparisons, we used multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between race, sex, age, end-stage renal disease (ESRD) and body mass index at diagnosis according to histological subtype.



Results

The RCC subtype distribution was significantly different in black people from that in white people (P < 0.001), with a substantially higher proportion of patients with papillary RCC among black people than white people (35.7 vs 13.8%). In multivariate analyses, compared with clear-cell RCC, people with papillary RCC were significantly more likely to be black (OR 4.15; 95% CI 2.64–6.52) and less likely to be female (OR 0.60; 95% CI 0.43–0.83). People with chromophobe RCC were significantly more likely to be female (OR 2.32; 95% CI 1.44–3.74). Both people with papillary RCC (OR 6.26; 95% CI 2.75–14.24) and those with chromophobe RCC (OR 7.07; 95% CI 2.13–23.46) were strongly and significantly more likely to have ESRD, compared with those with clear-cell RCC.



Conclusion

We observed marked racial differences in the proportional subtype distribution of RCCs diagnosed at a large tertiary care academic centre. To our knowledge, no previous study has examined racial differences in the distribution of RCC histologies while adjusting for ESRD, which was the factor most strongly associated with papillary and chromophobe RCC compared with clear-cell RCC.

Renal cell cancer histological subtype distribution differs by race and sex

Malignant tumors of the kidney and renal pelvis together rank 8th in cancer incidence and 12th in cancer mortality in the United States, with over 64,770 new cases and 13,570 deaths estimated for 2012.1 Over 90% of these tumors are adenocarcinomas, originating in the renal parenchyma (renal cell carcinoma (RCC)).2 RCC incidence has been rising substantially for at least four decades, with more rapid increases and emerging higher rates among black than white Americans since the mid-1990s.3 Whereas rates for tumors of all stages and sizes have risen, the majority of the increases since the 1980s have occurred in localized tumors, especially those <2.0 cm.2,4 In contrast, mortality from kidney cancer has leveled since the 1990s, with similar death rates between black and white Americans.5

Tumor stage and size are well documented to influence cancer prognosis.6,7 Tumor histological subtype has also been evaluated as a prognostic indicator for RCC patients.8–11 While papillary or chromophobe RCC have been shown to confer a better prognosis than clear cell RCC, the predominant subtype,9,10,12 histological subtype was not found to be an independent prognostic indicator in other studies.8,9,13 Few studies that have examined histological subtype among racially diverse populations have found that compared to whites, blacks have a lower percentage of clear cell RCC and a higher percentage of the papillary subtype.14 It remains unclear, however, whether racial differences in histological subtype distributions have contributed to overall racial differences in survival of RCC patients. Compared to white RCC patients, black patients have been shown to have a poorer prognosis despite their generally younger age and earlier tumor stage at diagnosis.15 Some studies attributed the survival disadvantage among black patients, in part, to differential access to surgical treatment,16,17 while others have contended that the racial disparity in survival cannot be explained by access to nephrectomy.18,19 To better understand racial differences in survival, we examined the survival patterns of RCC patients reported to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program by demographic characteristics and tumor stage, size, histological subtype, and surgical treatment.

/pdf/racial-disparity-in-renal-cell-carcinoma-patient-survival-4r73anu17f.pdf

Racial disparity in renal cell carcinoma patient survival according to demographic and clinical characteristics

In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age-adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001–2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies.

Using national data, we observed a higher proportion of black renal cell carcinoma (RCC) cases with papillary histology compared to Caucasian cases. We also observed time trends in black-white incidence differences in histologic RCC subtypes, with rapid increases in the disproportionate share of black cases with papillary histology.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.110

Racial difference in histologic subtype of renal cell carcinoma.

To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case-control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case-only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case-control analyses were performed to compute subtype-specific ORs for other risk factors using polytomous regression. In case-only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1-1.4 per 10-year increase), less likely to be female (OR = 0.5, 95% CI = 0.4-0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8-3.9) as compared to clear cell cases (N = 1,524). In case-control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1-1.3 per 5 kg/m(2) increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1-1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0-1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity-RCC association differs by histology.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.27934

An investigation of risk factors for renal cell carcinoma by histologic subtype in two case-control studies.

Background: Advanced renal cell carcinoma (RCC) results in over 14,000 deaths each year in the United States alone. The therapeutic landscape for advanced RCC changed dramatically with the approval of tyrosine kinase inhibitors (TKI) between 2006 and 2012. A large-scale analysis of survival trends has not been performed in the TKI era to determine their impact on outcomes for advanced RCC patients.
 Methods: The Surveillance, Epidemiology and End-Results (SEER) database was queried for adult patients with advanced RCC diagnosed between 2000 and 2013. Patients were divided into two cohorts based on the year of diagnosis—pre-TKI cohort [2000–2006] and TKI cohort [2007–2013]. Kaplan-Meier survival and multivariate Cox proportional hazards analyses were performed.
 Results: A total of 14,976 patients were included in our study. Median age at diagnosis was 64 years (range, 18–89 years). Median (cancer-specific) overall survival was 10.0 months in the TKI cohort compared with 8.0 months in the pre-TKI cohort, corresponding to a 13% improvement in survival in the TKI area [hazard ratio (HR) for death 0.87; 95% confidence interval (CI), 0.84–0.91, P<0.0001]. Median survival was improved by 2 months for patients with clear-cell RCC histology [HR for death 0.86; 95% CI, 0.84–0.91, P<0.0001]. Patients with non-clear cell RCC had a 25% higher risk of mortality compared with those with clear-cell RCC. Additionally, median survival for non-clear cell RCC patients was not statistically different between the two cohorts (HR for death 0.98; 95% CI, 0.88–1.09, P=0.714). Subgroup analysis showed that elderly patients (age 71 years and above) had a 45% higher risk of death from advanced RCC compared with young patients (aged 18–50 years) [HR for death 1.45; 95% CI, 1.36–1.54, P<0.0001]. Gender and racial disparities in outcomes were also noted with women having a 10% higher risk of death compared with men (HR for death 1.10; 95% CI, 1.06–1.14, P<0.001) and Black patients having a 15% higher risk of death compared with White patients (HR for death 1.15; 95% CI, 1.08–1.23, P<0.0001).
 Conclusions: Our study provides a largest registry-based analysis of survival outcomes in the TKI era. In majority of patients, the survival has improved significantly with the advent of TKIs as standard of care therapy. Survival for patients with non-clear cell RCC is clearly worse than clear-cell RCC and does not appear to have changed with TKIs. Elderly patients, women, and Black patients appear to have worse outcomes and these disparities merit further investigation.

/pdf/survival-outcomes-for-advanced-kidney-cancer-patients-in-the-5akc7fgy5c.pdf

Survival outcomes for advanced kidney cancer patients in the era of targeted therapies

Purpose: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC) between black and non-black patients in an equal-access health care system. Materials and Methods: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. Results: 204 kidney tumors were identified (Table-1). Of these, 117 (57.4%) were in black patients and 87 (42.6%) were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%), papillary RCC in 65 cases (31.9%), chromophobe RCC in 13 cases (6.4%), collecting duct/medullary RCC in 2 cases (1.0%), RCC with multiple histological subtypes in 8 cases (3.9%), malignant tumors of other origin in 6 cases (2.9%), and benign histology in 13 cases (6.4%). Among black patients, papillary RCC was seen in 56 cases (47.9%), compared to 9 cases (10.3%) among non-black patients (p < 0.001) (Table-2). Clear cell RCC was present in 38 (32.5%) of black patients and in 59 (67.8%) of non-blacks (p < 0.001). Conclusions: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

/pdf/rate-of-renal-cell-carcinoma-subtypes-in-different-races-4soqpnpsko.pdf

Rate of renal cell carcinoma subtypes in different races.

There is growing evidence that vaccines against SARS-CoV-2 can cause various skin reactions, many of which have autoimmune origins. These specific vaccine-induced autoimmune conditions with cutaneous manifestations include lupus erythematosus, bullous pemphigoid, vitiligo, alopecia areata, and leukocytoclastic vasculitis (LCV). In particular, LCV, which is also called hypersensitivity vasculitis, is an inflammation of small blood vessels. We present a case of an 81-year-old male evaluated in the emergency department for a bilateral purpuric non-blanching rash that appeared ten days after receiving the Pfizer-BioNTech booster vaccine against SARS-CoV-2. Results of a skin biopsy indicated LCV, and the rash completely resolved three weeks after clinical presentation.

/pdf/a-rare-cutaneous-manifestation-leukocytoclastic-vasculitis-387inkue.pdf

Hongbei Wang

Papers

Rate of renal cell carcinoma subtypes in different races.

A Rare Cutaneous Manifestation: Leukocytoclastic Vasculitis after Pfizer-BioNTech COVID-19 Vaccination