ObjectiveTo investigate the association of comprehensive control of multiple metabolic risk factors with the risk of all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease （MASLD） and its quantitative effect. MethodsA retrospective cohort study was conducted based on the data from National Health and Nutrition Examination Survey （NHANES） in 2003—2018. A total of 29 458 participants were enrolled， including 12 528 patients with MASLD and 16 930 non-MASLD controls. The control status of nine risk factors was assessed， i.e.， hypertension， diabetes， liver fibrosis （assessed by fibrosis-4 index ［FIB-4］）， aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio， serum albumin， renal function （assessed by serum creatinine）， systemic inflammation （assessed by neutrophil count）， smoking， and physical activity. According to the status of comprehensive risk factor control， the patients with MASLD were further divided into low-control group with 1 107 patients， moderate-control group with 7 042 patients， and high-control group with 4 379 patients. A total of 397 participants were enrolled in the external validation cohort， among whom there were 266 participants with MASLD and 131 participants without MASLD. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test was used for comparison of categorical data between groups. The Cox proportional hazards model incorporating complex sampling weights for NHANES data were used to investigate the association between the degree of risk factor control and all-cause mortality， and the Kaplan-Meier curve， the log-rank test， restricted mean survival time （RMST）， and population attributable fraction （PAF） were used for further assessment. The robustness of the findings was validated in an independent clinical cohort （n=397）. ResultsThe cohort study based on the NHANES database showed that during the median follow-up time of 6.7 years， 1 171 deaths occurred among the 12 528 patients with MASLD. There was a significant reduction in mortality risk with the increase in the number of risk factors controlled （trend test： χ²=65.06， P<0.001）. Compared with the low-control group， the mortality risk decreased successively in the moderate-control group （hazard ratio ［HR］=0.59， 95% confidence interval ［CI］： 0.51 — 0.69） and the high-control group （HR=0.36， 95%CI： 0.27 — 0.48）， and the mortality risk was reduced by 22% for each additional risk factor controlled （HR=0.78， 95%CI： 0.74 — 0.82）. The PAF analysis showed that AST/ALT ratio control （PAF=19.2%） and physical activity （PAF=18.9%） were the largest contributors. The survival analysis of the sub-cohort constructed based on nearest neighbor matching （with a maximum follow-up time of 13.3 years） showed that there was a significant difference in cumulative survival rate between the MASLD groups with different control levels and the non-MASLD group （P<0.001）. The RMST analysis further quantified the survival benefit of each group， and the high-control group had the longest 10-year RMST （9.88 years）， which was superior to that of the non-MASLD group （9.43 years）， the moderate-control group （9.33 years）， and the low-control group （7.96 years）. The multivariable-adjusted model analysis of the complete cohort showed that compared with the non-MASLD population， the MASLD patients in the low-control group had a significant increase in mortality risk， the moderate-control group had a comparable mortality risk， and the high-control group had a significantly lower mortality risk. The subgroup analysis showed a significant protective effect of comprehensive control in both male and female individuals （P<0.05）， and the interaction analysis suggested a potentially stronger protective effect in female individuals （P_{for interaction}=0.031）. The protective effect was statistically significant in patients aged ≥60 years （P<0.05）. There was a significant difference in protective effect across the groups stratified based on waist circumference （P<0.05）， but there was no significant interaction between groups （P_{for interaction}=0.821）. In the external validation cohort， among the 397 participants， there were 72 cases of all-cause mortality （18.1%）. The survival analysis showed a significant gradient increase in the survival rate of MASLD patients with the increase in the level of control （P=0.022）. The RMST analysis showed that the moderate- and high-control groups had a better RMST than the non-MASLD group at 5 years （4.47 years vs 4.56 years vs 4.40 years）， with a more significant survival advantage at 10 years （8.67 years vs 8.95 years vs 8.44 years）. The Cox regression analysis showed that， with the low-control MASLD group as the reference， there was a significant reduction in mortality risk in the moderate-control group （HR=0.41， 95%CI： 0.21 — 0.81） and the high-control group （HR=0.32， 95%CI： 0.14 — 0.71）； with the non-MASLD population as the reference， there was a significant increase in mortality risk in the low-control group （HR=2.02， 95%CI： 1.03 — 3.95）， with a comparable mortality risk in the moderate-control group （HR=0.83， 95%CI： 0.48 — 1.44） and the high-control group （HR=0.66， 95%CI： 0.30 — 1.38）， and the point estimates of the effects were highly consistent with the main study. ConclusionAmong MASLD patients， better control of metabolic risk factors is associated with a lower mortality risk. Achieving optimal control can eliminate the excess mortality risk associated with MASLD， thereby helping patients achieve a better survival prognosis than the general population.

Objective: To investigate the clinicopathologic features, diagnostic and differential diagnostic aspects of pigmented microcystic chromophobe renal cell carcinoma (ChRCC). Methods: Five cases of pigmented microcystic ChRCC were collected at Zhejiang Provincial People′s Hospital from January 2013 to January 2018. The clinical features, gross and histological appearances, immunohistochemistry and prognosis were analyzed and the relevant literature was reviewed. Results: There were 3 men and 2 women with age range of 45 years to 72 years (mean 57 years). All tumors were incidentally identified by imaging examinations. Grossly, the tumors were well-demarcated and showed diameters ranging from 1.8 cm to 4.0 cm(mean 2.9 cm). On cross section, the tumors were brown to gray tan with solid cut-surface mixed with multiple cysts of variable sizes. Hemorrhage was common, central scar was not seen. Microscopically, the tumors were composed predominantly of irregular and variable-sized microcystic or tubulocystic patterns, with extensive cribriform structures formation and focal adenomatous rearrangements seen in one case each, and focal pseudo-papillary structures (lacking true fibro-vascular cores) seen in two cases. Microscopic calcifications and psammoma bodies were present in all tumors. Four tumors composed mostly of eosinophilic cells whereas 1 predominated in plant-like cells. Brown pigmentations, either intracytoplasmic or extracytoplasmic, were noted in all five cases. The tumor cells had irregular, low-grade nuclei (Paner grade: 1) frequently with binucleation and perinuclar halos. Tumor necrosis or sarcomatous transformation was not seen. By immunohistochemistry, the tumor cells expressed CK, EMA, and E-cadherin diffusely and strongly in five cases; and CK7 and CD117 diffusely in four cases. They were negative for vimentin, CD10, CA9, AMACR/P504s, TFE3, HMB45, Melan A, S-100 protein, synaptophysin and chromogranin. Partial nephrectomies were performed for all five patients; there was no tumor recurrences or metastases at a follow-up of 2 to 55 months (mean, 17 months). Conclusions Pigmented microcystic ChRCC is a rare histological variant of ChRCC with relatively indolent behavior, and shows morphologic heterogeneity which can elicit a wide range of differential diagnoses. Careful attentions to search for typical features of classic ChRCC with the use of immunohistochemistry can help to distinguish this tumor from its many mimickers.

Objective: To investigate the clinicopathologic characteristics, immunophenotypes, and differential diagnostic features of extra-pleural solitary fibrous tumor (SFT) with uncommon histology. Methods: Seven cases of extra-pleural SFT with uncommon histology were collected during January 2015 and December 2016 in Zhejiang Provincal People′s Hospital; the clinical and radiologic features, histomorphology, immunophenotype and prognosis were analyzed. EnVision method was used for immunohistochemical staining of STAT6, CD34 and other differential diagnosis associated markers. Results: There were five male and two female patients, age from 23 to 54 years (mean=39 years). Three tumors were located in the soft tissue of head and neck, two in trunk subcutaneous soft tissue, one in sella region, and one in the kidney. Grossly the tumors ranged from 0.4 to 8.0 cm (mean=3.1 cm). Microscopically, all three head and neck cases resembled giant cell angiofibroma/giant cell subtype SFT, and one case showed sheet-like pattern of the multinucleated syncytial cells, creating a biphasic arrangement similar to myofibroma. Both truncal tumor resembled lipomatous type SFT, with one similar to dermatofibrosarcoma protuberans and the other to atypical spindle cell lipomatous tumor. The sella tumor showed morphology of a conventional SFT with high grade sarcomatous transformation. The renal tumor demonstrated a malignant SFT with entrapped benign renal tubules, mimicking a biphase synovial sarcoma or a malignant mixed epithelial and stromal tumor. By immunohistochemistry, all seven SFTs showed diffuse and strong nuclear reactivity to antibody against STAT6. Conclusions Extra-pleural SFTs show a significant heterogeneity of morphology and biological behavior which could cause differential confusion.Careful attention to its characteristic histomorphology with the use of STAT6 immunohistochemistry can help distinguish this tumor from its many mimickers.