OBJECTIVE: To analyze the clinical and histological characteristics of small renal carcinoma (diameter ≤100 px), and to provide theoretical basis for the safety and effectiveness of kidney unit preservation surgery and judgment of prognosis. METHODS: The pathological data of 490 small kidney cancer patients admitted from May 2000 to October 2014 were retrospectively analyzed to record the characteristics of tumor size, pathological type, Fuhrman classification, pathological stage, tumor multifocality, venous tumor thrombus, tumor pseudo-envelope, hemorrhagic necrosis, and distant metastasis. The tumor diameters ranged from 0.6 to 100 px, with an average of (3.2±0.6) cm. 422 cases (86.1%) were clear cell carcinoma, 32 cases (6.5%) were suspicious cell carcinoma, 23 cases (4.7%) were papillary carcinoma, and 13 cases (2.7%) were mixed cell and other rare types. 422 cases of clear cell carcinoma included 27 cases of Fuhrman grade I, 157 cases of grade I-II, 210 cases of grade II-III, and 21 cases of grade II-III. 210 cases, 21 cases of grade II-III, 7 cases of grade III, and 0 cases of grade IV. There were 18 cases (3.7%) of multifocal tumors and 6 cases (1.2%) of renal vein tumor embolism. 326 cases (66.5%) of tumors had complete pseudo-envelope with thickness of 0.2-1.0 mm. 82 cases (16.7%) of tumors infiltrated but did not penetrate the pseudo-envelope, 11 cases (2.2%) penetrated the pseudo-envelope, 9 cases (1.8%) invaded the extra-envelope fat, 240 cases (48.9%) were associated with hemorrhagic necrosis. Logistic regression analysis showed that tumor infiltration and penetration of the pseudo-envelope correlated with Fuhrman II-III and III grading and tumor diameter (P=0.04), tumor size correlated with histologic grading and renal envelope invasion (P=0.02), and did not correlate with renal vein tumor thrombosis and multifocality (P=0.35). CONCLUSION: The vast majority of small renal carcinomas are highly differentiated and low malignancy, but very few can invade perirenal fat or even develop distant metastases at an early stage, with significant heterogeneity. Most small renal carcinomas have obvious pseudo-envelope, and tumors with diameter >3.0 cm and high Fuhrman grade are more likely to invade the pseudo-envelope or even perirenal fat, and the adipose tissue on the surface of the tumor should be removed at the same time for surgery to preserve the renal unit. Subjects and methods Pathological and clinical data of 490 cases of small renal carcinoma, in which the general presentation, pathological type, Fuhrman grading, tumor pseudo-envelope and local invasion were obtained from archived pathological reports. I. Clinical data There were 490 cases in this group, 367 males and 123 females, aged 17 to 85 years, with an average of (62.7±11.4) years. The patients were examined preoperatively by ultrasound, CT and intensification or MRI, and none of the patients with hereditary renal cancer were included in this study. Clinical manifestations were 28 cases of carnal hematuria, 78 cases of microscopic hematuria, 46 cases of lumbar discomfort, and 338 cases found by physical examination or other disease examinations. Three of the patients were diagnosed with pulmonary metastasis of kidney cancer when multiple nodules in the lung were found on preoperative chest X-ray or chest CT. The tumor diameters ranged from 0.6 to 100 px, with an average of (3.2±0.6) cm, of which 37 cases were <50 px, 110 cases were 2.0-75 px, and 343 cases were 3.1-100 px. Among the 490 cases, 132 cases underwent renal unit preservation surgery and 358 cases underwent radical nephrectomy. The pathological data were examined to observe the tumor site, whether there were multicenter lesions inside the cut surface, the integrity of tumor pseudo-envelope and infiltration of renal parenchyma outside the pseudo-envelope, whether there were combined renal vein tumor emboli and local enlarged lymph nodes. The tumor and the kidney tissues around the tumor, especially the suspicious parts observed by the naked eye, were taken, fixed with 10% formaldehyde, and then serially sectioned with conventional paraffin embedding and HE staining, and all specimens were observed and analyzed by two pathologists from Tianjin Institute of Urology. The histological classification of renal tumors was based on WHO 2004 version, Fuhrman grade I and II were highly differentiated (G1), grade III was moderately differentiated (G2), and grade IV was poorly differentiated or undifferentiated (G3). Tumor pseudo-envelope is defined as tumor growth extruding surrounding renal parenchyma and surrounding proliferating tissues to form a dense membranous tissue, mainly composed of normal renal parenchyma and proliferating fibrous tissues. Renal cancer multifocality was defined as any malignant lesion outside the pseudo-envelope of the primary renal tumor, while multiple nodules within the pseudo-envelope were not considered as multifocality. The integrity of the pseudo-envelope, the extent of tumor infiltration, tumor multifocality and satellite lesions were observed microscopically. The pathological information such as tumor size, pathological stage, grading and the presence of necrotic cystic lesions were recorded completely. Statistical treatment SPSS 19.0 software was used to statistically analyze the obtained data, and the count data were expressed as rate (%), and the measurement data were expressed as mean ± standard deviation. x2 test and Fisher's exact probability method were used to compare the rates between groups, and multi-factor logistic regression analysis was applied for correlation analysis. p<0.05 was considered as statistically significant difference. Results There were 490 cases of small kidney cancer in this group, and 422 cases (86.1%) were pathologically diagnosed as clear cell carcinoma, 32 cases (6.5%) as suspicious cell carcinoma, 23 cases (4.7%) as papillary carcinoma, and 13 cases (2.7%) as mixed cell and other rare types. Among the clear cell carcinomas, 27 cases were Fuhrman grade I, 139 cases were grade I-II, 228 cases were grade II, 21 cases were grade II-III, 7 cases were grade III, and 0 cases were grade IV. There were 18 cases (3.7%) of multifocal or multiple tumors, 6 cases (1.2%) with renal vein tumor embolism, and 240 cases (48.9/%) with hemorrhagic necrosis and cystic changes in the tumor. The tumors had intact pseudo-envelope in 326 cases (66.5%) and lacked intact pseudo-envelope in 164 cases (33.5%), among which 122 cases had limited defect and discontinuity of pseudo-envelope and 42 cases had no typical pseudo-envelope. According to the relationship between tumor and pseudo-envelope under the microscope, they could be classified into 3 types: uninfiltrated envelope, infiltrated envelope and penetrated envelope. Among them, 82 cases (16.7%) had tumor infiltration into the pseudo-envelope, 11 cases (2.2%) had tumor penetration into the pseudo-envelope, and 9 cases (1.8%) had tumor invasion into the extra-envelope perirenal fat. The thickness of the pseudo-envelope of the tumor was 0.2-1 mm, and the typical pseudo-envelope was mainly composed of fibrous tissue with a small amount of lymphocytic infiltration under the microscope. Logistic regression analysis showed that infiltration and penetration of the pseudo-envelope correlated with Fuhrman II-III and III grading and tumor diameter (P=0.04). There was a correlation between tumor size and histologic grade and renal envelope invasion (P=0.02), but not between renal vein tumor thrombosis and multifocality (P=0.35). Discussion It is currently believed that most small renal cancers (≤4 cm) are well differentiated, have a low clinical stage, slow natural growth rate and a better prognosis. Nephron sparing surgery (NSS) for small renal carcinoma is safe and reliable with low recurrence and mortality, and a meta-analysis demonstrated that NSS reduced the incidence of postoperative chronic kidney disease by 61% and mortality by 19% compared with radical nephrectomy [1]. Therefore, NSS has become the main treatment for stage T1a kidney cancer. However, small renal carcinomas are significantly heterogeneous, and a few show infiltrative growth and can metastasize early [2]. Therefore, it is of great clinical significance to systematically study the histological characteristics of small kidney cancer and screen the risk factors for recurrence and progression of small kidney cancer to reasonably select surgical methods. In conclusion, small renal carcinoma has obvious heterogeneity, most of them have obvious pseudo-envelope and are highly differentiated, low malignant tumors with good biological behavior, but very few of them have invasive growth characteristics or even can metastasize in early stage. The extent of surgical resection should be considered according to the intactness of pseudo-envelope, the extent of infiltration, the multifocality of tumor, the presence of tumor embolus and metastasis, etc.