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Despite the considerable progress made in our understanding of the pathogenesis, genetics, and pathology of renal cell carcinoma (RCC), difficulties remain relating to the prediction of clinical outcome for individual cases. Although there is evidence to show that high-grade tumors have a poorer prognosis when compared to those of low grade, debate remains regarding the predictive value of grading, especially for those tumors classified into the intermediate grades. Numerous composite morphologic and nuclear grading systems have been proposed for RCC and although that of the Fuhrman classification have achieved widespread usage, the validity of the grading criteria of this classification has been questioned. In addition, there are few studies that have attempted to validate the Fuhrman system for RCCs beyond that of the clear cell subtype. Recent studies have indicated that grading of papillary RCC should be based on nucleolar prominence alone and that the components of the Fuhrman grading classification do not provide prognostic information for chromophobe RCC. Independent of tumor grade, the prognostic importance of tumor stage for RCC is well recognized. The Union Internationale Contre le Cancer/American Joint Committee for Cancer Staging and End Results Reporting TNM staging system is now in its sixth edition (2002) and recent refinements have focused on defining size cut points that will identify apparently localized tumors that will develop recurrence and/or metastases despite attempted curative surgery. In parallel with these studies it has been shown that infiltration of the renal sinus is an important prognostic factor, being observed in almost all tumors >7 cm in diameter. Questions remain as to the appropriate stratification of regional extension of RCC, as defined in the T3 tumor-staging category. Recent modifications to this category have been suggested combining the level of infiltration of the venous outflow tract with the presence or absence of infiltration of the adrenal gland and/or perirenal fat. Similarly, the utility of classifying lymph node involvement by tumor is debated, although it is well recognized that lymph node infiltration is associated with a poor prognosis. Although the current TNM classification does provide useful prognostic information it would appear that further modifications are justified to enhance the predictive value of staging for RCC.Modern Pathology (2009) 22, S24–S36; doi:10.1038/modpathol.2008.183

Locally advanced breast cancer encompasses a heterogeneous collection of breast neoplasms and constitutes approximately 10%‐20% of the newly diagnosed breast cancers. These cancers may have widely different clinical and biological characteristics. Patients with these tumors may be classified as stage IIB, III or IV breast cancer according to the American Joint Committee for Cancer Staging and End Results Reporting (TNM classification). Multidisciplinary therapy has become the treatment of choice for these patients. Primary or neoadjuvant chemotherapy followed by locoregional therapy, either surgery and/or radiotherapy, and postoperative systemic chemotherapy is now an accepted strategy. More than 70% of patients achieve an objective response (including pathological complete remission in 10%‐25% of cases), and many patients experience downstaging through primary chemotherapy. Breast conservation is possible in 10%‐40% of patients with locally advanced breast cancer; almost all patients initially are rendered disease‐free, and long‐term local control is achieved in over 70% of these patients. Primary chemotherapy is the initial choice of treatment for patients with locally advanced tumors, but it is unclear what the optimal sequence of subsequent therapies should be, whether one or two local treatment modalities are necessary, and whether any or different postoperative chemotherapy is needed. The efficacy of primary chemotherapy was demonstrated in several large prospective studies in patients with locally advanced breast cancer. The natural history of this disease was changed dramatically by the introduction of these combined modality therapies. Five‐year disease‐free survival rates of 35%‐70% are commonly reported, and about 25%‐40% of patients will survive beyond 10 years without recurrence. In summary, multidisciplinary therapy that includes primary chemotherapy provides appropriate local control and the possibility of breast conservation therapy; it increases surgical resectability and survival rates in patients with locally advanced breast cancer. The role of new innovative therapeutic strategies such as high‐dose chemotherapy, with hematopoietic stem cell rescue, new cytotoxic agents and higher dose‐intensity therapy is currently under evaluation in patients with locally advanced breast cancer.