Maria F. Serrano

Utility of high molecular weight cytokeratins, but not p63, in the differential diagnosis of neuroendocrine and basaloid carcinomas of the head and neck

High-grade neuroendocrine carcinomas of the head and neck overlap significantly in morphology with both basaloid squamous and solid-type adenoid cystic carcinomas. High-grade neuroendocrine carcinomas have sheets of small cells with scant cytoplasm, granular chromatin, and inconspicuous nucleoli. Basaloid squamous and adenoid cystic carcinomas are aggressive variants of their respective tumor types which both have nests of basaloid tumor cells with round nuclei, little cytoplasm, and inconspicuous nucleoli. As the management and prognosis of these tumors are very different, it is important to differentiate them. We performed high molecular weight cytokeratin (CK) and p63 immunohistochemistry on 19 neuroendocrine carcinomas, 18 basaloid squamous carcinomas, and 11 solid-type adenoid cystic carcinomas. All tumors were immunostained for p63, CK 34betaE12, CK 5/6, synaptophysin, chromogranin-A, S-100, and smooth muscle actin. All basaloid squamous and adenoid cystic carcinomas were positive for CK 5/6 and 34betaE12. Only 4 and 5 of the 19 neuroendocrine carcinomas, respectively, were positive for these markers. Staining was focal in the neuroendocrine cases when positive, whereas almost all basaloid squamous and adenoid cystic carcinomas showed strong staining. Almost all tumors of each type were positive for p63, including neuroendocrine carcinomas, but with different staining patterns. Basaloid squamous carcinomas were diffusely positive, neuroendocrine carcinomas were diffusely positive, but with weak staining, and adenoid cystic carcinomas showed a distinct pattern with staining at the periphery of the cell nests only. We conclude that high molecular weight cytokeratin immunostaining is helpful in distinguishing high-grade neuroendocrine carcinomas from similar tumor types.

Impact of Comorbidity on Overall Survival in Patients Surgically Treated for Renal Cell Carcinoma

OBJECTIVES Although the classification of cancer has traditionally focused on the gross and microscopic characteristics of the tumor, the overall health of patients can affect their survival. Because patients with renal cell carcinoma often have other medical conditions, we explored the effect of preexisting medical disease on survival after radical and partial nephrectomy. METHODS From January 1995 to August 2003, the comorbidity status of 697 patients with nonmetastatic renal cell carcinoma who had undergone radical or partial nephrectomy was prospectively coded using the Adult Comorbidity Evaluation-27. Histopathologic review of all slides was performed according to the 2004 World Health Organization scheme. Other variables analyzed included age, sex, ethnicity, pathologic stage, Fuhrman grade, and tumor size. The effect of these factors on overall survival (OS) was analyzed using Cox proportional hazards regression model. RESULTS The median follow-up was 32.2 months for survivors and 36.5 months for all patients. The OS rate at 1, 3, and 5 years was 92.0% (641 patients), 75.3% (525 patients), and 52.7% (367 patients), respectively. Univariate analyses demonstrated that age, comorbidity, tumor size, Fuhrman grade, and pathologic stage were significant predictors of OS. Multivariate analysis revealed that age (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.10 to 1.82, P = .0067), comorbidity (HR 1.37, 95% CI 1.16 to 1.63, P = .0002), pathologic stage (HR 1.97, 95% CI 1.60 to 2.41, P < .0001), and grade (HR 1.83, 95% CI 1.28 to 2.59, P = .0008) predicted for OS. CONCLUSIONS The results of this study have demonstrated that comorbidity is an independent prognostic factor for OS in patients with renal cell carcinoma. Capturing the comorbidity information using validated instruments can improve the preoperative evaluation of patients by providing more accurate prognostic information.

The role of lymphovascular space invasion in renal cell carcinoma as a prognostic marker of survival after curative resection.

OBJECTIVES Lymphovascular invasion (LVI) correlates with adverse outcomes in numerous malignancies. However, its role in predicting outcomes in RCC is unclear. Herein, we evaluated what effect LVI had on metastasis free survival (MFS), disease-specific survival (DSS), and overall survival (OS) in patients with RCC treated with surgical excision. METHODS Eight hundred forty-one consecutive patients who underwent partial or radical nephrectomy from 1989 to 2004 were identified. Pathologic and gross features examined were LVI, subtype, Fuhrman grade, stage, and size. Age and gender were also analyzed. Slides were re-reviewed by a single pathologist (MS). Variables with P < 0.1 on univariate analysis were incorporated in a Cox proportional hazards multivariate model. MFS, DSS, and OS were described for patients with and without LVI using the Kaplan-Meier method, and compared with the log-rank test. RESULTS LVI was seen on H and E stained slides in 91 patients (11%); 120 (14%) developed metastatic disease, 91 (11%) died of RCC, and 306 (36%) died during a median follow-up of 61 months. While on univariate analysis, LVI was strongly associated with decreased MFS, DSS, and OS (P < 0.0001), on multivariate analysis, LVI was no longer statistically significant for MFS, DSS, and OS with a HR of 0.976 (95% CI: 0.583-1.63; P = 0.93), 0.96 (95% CI: 0.542-1.69; P = 0.88), and 1.24 (95% CI: 0.869-1.77; P = 0.24). CONCLUSIONS We found LVI to be associated with worse MFS, DSS, and OS on univariate analysis, but not on multivariate analysis for patients with nonmetastatic RCC. In contrast to previously reported studies, LVI may not be an independent prognostic variable in patients with localized RCC.

Percent Microscopic Tumor Necrosis and Survival After Curative Surgery for Renal Cell Carcinoma

PURPOSE Tumor necrosis is a potential marker of recurrence and survival after surgery for renal cell carcinoma. We determined whether a correlation exists between the amount (not just the presence/absence) of tumor necrosis, and metastasis-free, disease specific and overall survival after surgery for renal cell carcinoma. MATERIALS AND METHODS We identified 841 consecutive patients who underwent partial or radical nephrectomy from 1989 to 2004 for renal cell cancer. Specimens were re-reviewed by a single pathologist (MFS). The tumor necrosis percent was none in 586 cases, less than 50% in 198 and 50% or greater in 55. Grade, stage, subtype, size, gender and age were also analyzed. Variables at p <0.05 on univariate analysis were incorporated into a Cox proportional hazards multivariate model. Metastasis-free, disease specific and overall survival was described using the Kaplan-Meier method and compared with the log rank test. RESULTS Tumor necrosis was found in 253 specimens (30%). Univariate analysis revealed that the percent and presence of tumor necrosis correlated with metastasis-free, disease specific and overall survival. On multivariate analysis tumor necrosis presence/absence did not remain an independent predictor of disease specific (p = 0.7), metastasis-free (p = 0.7) or overall (p = 0.2) survival. Greater than 50% tumor necrosis was no longer a statistically significant predictor of metastasis-free survival (p = 0.45) but remained significant for disease specific (p = 0.02) and overall (p = 0.01) survival. CONCLUSIONS The presence of 50% or greater tumor necrosis correlates with worse disease specific and overall survival but not metastasis-free survival in patients with renal cell carcinoma. Results support the inclusion of percent tumor necrosis over the presence/absence of tumor necrosis in the risk assessment of patients who undergo surgical treatment for renal cell carcinoma.

Effect of Reclassification on the Incidence of Benign and Malignant Renal Tumors

PURPOSE The incidence of benign renal tumors has increased in recent years. This trend is commonly attributed to the increased use of cross-sectional imaging and minimally invasive surgical approaches. An alternative hypothesis is that recent changes in histological classification are responsible for the increasing incidence. To further investigate the impact of histological reclassification we reexamined all excised renal masses using the 2004 WHO criteria and compared this histological classification to the prior criteria. MATERIALS AND METHODS We identified 1,101 consecutive partial and radical nephrectomy cases managed at our institution from 1989 to 2003. All histopathological sections were rereviewed by a single pathologist and reclassified according to 2004 WHO criteria. The percentages of benign lesions per year according to the prior histological and current WHO 2004 histological criteria were compared. RESULTS Of the 1,101 renal masses 132 (12.0%) and 165 (15.0%) were classified as benign using prior and current WHO criteria, respectively. On average the WHO criteria diagnosed more benign tumors per year than the prior criteria (p = 0.004). Linear regression demonstrated a similar, persistent increase in benign diagnoses per year of 0.69% (WHO) and 1.22% (prior) during the 14-year period (p = 0.33). All masses reclassified as benign were oncocytoma (33). CONCLUSIONS Implementation of the 2004 WHO criteria is contributing to the increase in diagnosis of benign renal lesions, specifically oncocytoma. Changes in histological classification do not account for the entire increase. Other factors, which remain to be delineated, are also contributing to the increase in the diagnosis of benign renal lesions.

DOES PERCENT HIGH GRADE CORRELATE WITH SURVIVAL FOLLOWING SURGERY FOR RENAL CELL CARCINOMA

1201 DOES PERCENT HIGH GRADE CORRELATE WITH SURVIVAL FOLLOWING SURGERY FOR RENAL CELL CARCINOMA? Matthew D Katz*, Maria F Serrano, Yan Yan, Peter A Humphrey, Adam S Kibel. Saint Louis, MO. INTRODUCTION AND OBJECTIVE: It has been demonstrated that percent of high grade cancer correlates with survival for a wide variety of tumors. Recent work has demonstrated that the percentage of high grade cancer in prostatectomy specimens correlates with survival, raising the possibility that this pathologic parameter may provide prognostic information in other malignancies. Herein, we examine renal cell carcinoma (RCC) specimens to determine if a correlation exists between percentage of high grade tumor and metastasis-free survival