Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in The Era of Targeted Therapies and Personalized Medicine.

CONTEXT: The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and-with the exception of some rare tumors-the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. OBJECTIVE: To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. DATA SOURCES: Published literature and personal experience. CONCLUSIONS: In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains

Micropapillary Urothelial Carcinoma: A Clinicopathological Study of the Experience of One Academic Center

Background: Micropapillary variant of urothelial carcinoma (MPUC) is a rare UC variant. MPUC have been reported in the urinary bladder, ureter and renal pelvis. Its prognosis and treatment is controversial in the literature. Some studies showed the overall prognosis for MPUC is poor and suggest the early treatment with cystectomy. Whereas one study demonstrated that there is no considerable difference between micropapillary pattern positive and negative groups according to the progression rates in non-muscle-invasive and muscle-invasive groups. In this study, we tried to study the clinicopathological correlation of MPUC, particularly comparison to conventional urothelial carcinoma with same grades and same stages. Design: 23 MPUC, 135 low grade (LG) and 92 high grade (HG) UC are retrieved. The tumor stage, lymphatic invasion and metastasis including lymph node and distant organs are evaluated. Clinical follow-up is up to 8 years

Decreased p63 Expression Is Common in Micropapillary Urothelial Carcinoma (MPUC) and High Grade Urothelial Carcinoma (HGUC)

Background: In normal human tissues strong nuclear p63 protein expression is present in the basal layer of stratified squamous and transitional epithelia. Immunohistochemistry (IHC) for p63 is frequently used in clinical practice to aid in diagnosing urothelial carcinoma (UC). However, loss of p63 expression has been described in high stage UC. Micropapillary urothelial carcinoma (MPUC) is a variant of bladder cancer with an aggressive behavior that frequently presents at an advanced stage. The aim of our study was to investigate p63 IHC in MPUC in comparison to conventional UC of different grades and stages. Design: IHC for p63 expression was performed on paraffi n embedded tissue sections of 23 cases of HGUC, 20 cases of low grade urothelial carcinoma (LGUC) and 20 cases of MPUC. IHC staining was scored semiquantitatively as follows: 0 (no reactivity); 1+ (\u3c 10% cells labeling); 2+ (10 – 50% cells labeling); 3+ (50 – 75% positive); 4+ (75– 90% positive); and 5+ (\u3e 90% positive). Only nuclear labeling was considered positive. Results: p63 expression was identifi ed in non-neoplastic surface urothelium in all MPUC cases, however, the MPUC tumor cells were negative for p63 (Table 1). 22% of high stage (pT2 or pT3) HGUC were also negative for p63. Additionally, 22% of pT2 or pT3 HGUC showed only 1+ labeling. In contrast, 60% of low stage (pTis or pT1) HGUC exhibited more than 3+ labeling. Finally, 70% of LGUC exhibited 5+ (more than 90% tumor cells) labeling for p63