Renal Mass Imaging with MRI Clear Cell Likelihood Score: A User's Guide.

Small solid renal masses (SRMs) are frequently detected at imaging. Nearly 20% are benign, making careful evaluation with MRI an important consideration before deciding on management. Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with potentially aggressive behavior. Thus, confident identification of ccRCC imaging features is a critical task for the radiologist. Imaging features distinguishing ccRCC from other benign and malignant renal masses are based on major features (T2 signal intensity, corticomedullary phase enhancement, and the presence of microscopic fat) and ancillary features (segmental enhancement inversion, arterial-to-delayed enhancement ratio, and diffusion restriction). The clear cell likelihood score (ccLS) system was recently devised to provide a standardized framework for categorizing SRMs, offering a Likert score of the likelihood of ccRCC ranging from 1 (very unlikely) to 5 (very likely). Alternative diagnoses based on imaging appearance are also suggested by the algorithm. Furthermore, the ccLS system aims to stratify which patients may or may not benefit from biopsy. The authors use case examples to guide the reader through the evaluation of major and ancillary MRI features of the ccLS algorithm for assigning a likelihood score to an SRM. The authors also discuss patient selection, imaging parameters, pitfalls, and areas for future development. The goal is for radiologists to be better equipped to guide management and improve shared decision making between the patient and treating physician. © RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Pedrosa in this issue.

A novel aberration of COL1A1-PDGFB fusion as an insertion in chromosome 15 in one case of dermatofibrosarcoma protuberans involving a rare location.

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma of the skin arising from the dermis. Its location is most commonly presented on the trunk of middle-aged adults and rarely on the face. The characteristic genetic aberration in the form of a reciprocal translocation t(17;22)(q21;q13) or a ring fusing the COL1A1 and PDGFB genes is found in 90% of DFSP. We present a case of a 42-year-old man who presented with a DFSP on the left cheek with foci of myxoid-fibrosarcomatous transformation. A conventional chromosomal analysis revealed a complex karyotype without a supernumerary ring chromosome or a linear translocation t(17;22). Comparative genome hybridization and fluorescence in-situ hybridization revealed the fusion of COL1A1 and PDGFB probes inserted in chromosome 15. This is a unique case of DFSP characterized by a rare body location, unique histopathological features, and novel chromosome COL1A1-PDGFB insertion, and may help guide future diagnostic and patient care modalities.

PD-L1 expression in sarcomas: An immunohistochemical study and review of the literature.

BACKGROUND: Immunotherapy is increasingly used for treatment of metastatic melanoma and carcinomas. PD-1 (programmed death 1) and its associated ligand (PD-L1) inhibits the activation of T-lymphocytes. This inhibition can be impacted by a number of drugs. Response to these drugs is predicted by assessment of PD-L1 expression. PD-L1 expression varies between 19% and 92% in melanomas and carcinomas. PD-L1 expression is less well documented for sarcomas. DESIGN: Fifty-six sarcomas of various histopathologic types were immunohistochemically stained (IHC) for PD-L1 using the antibody clone SP263 (Ventana, Tuscan, AZ). Membrane staining of tumor cells was quantitated as a percentage of total tumor cells. Sarcomas were judged as non-expressors (less than 1%) low-expressors (1 to 50%) and high expressors (greater than 50%). The percentage of each type of sarcoma judged as an expressor was determined. RESULTS: Table 1 documents the percentage of each type of sarcoma expressing PD-L1. 14% of sarcomas expressed PD-L1. Percentage of sarcomas expressing PD-L1 varied significantly between types but the majority of sarcomas were non-expressors. CONCLUSION: PD-L1 IHC expression is valuable in predicting response to immune-modulating drugs. Such therapies may be useful for treatment of metastatic sarcomas. Expression of PD-L1 in carcinomas and melanomas is variable ranging from 19% to 92%. In our study, a minority (14%) of sarcomas expressed PD-L1. Other studies have shown similar results with between 1.4 and 59% (average 24%) of sarcomas expressing PD-L1. Expression appears to be sarcoma type specific. These finding suggest that PD-L1 based therapy may be less useful in sarcomas than in other malignancies.

Relationship between uric acid levels and progressive supranuclear palsy.

INTRODUCTION: The pathophysiology of both PD and PSP is characterized by a pro-oxidant state. Uric acid is an oxidative stress marker. High uric acid blood levels have been associated with a reduced risk of PD and a decreased rate of disease progression. We investigated whether a low serum concentration of uric acid is also associated with PSP. METHODS: We measured serum uric acid concentrations in a subsample of the ENGENE PSP Cohort that included 75 cases and 75 frequency-matched-by-sex healthy controls (69 spouses, 6 in-laws) from four centers willing to participate (Case Western, Rush University, University of Utah, and University of Louisville). Case severity was characterized using the total PSP-Rating Scale, UPDRS, and Mattis Dementia Rating Scale. Unconditional logistic regression, Pearson's chi-squared test, and analysis of variance were used, as appropriate. RESULTS: The mean uric acid level among cases (4.0 mg/dL) was not significantly lower than that of controls (4.1 mg/dL). When controlling for sex, there were no between-group statistical differences in uric acid levels. Uric acid levels were not correlated with disease severity. CONCLUSIONS: The results of this study do not provide evidence of uric acid having a protective role in PSP, even if oxidative injury is important in the pathophysiology of this disorder. The lack of statistical significance suggests that there is no direct association between uric acid levels and PSP. However, a small inverse association cannot be excluded. © 2016 Movement Disorder Society.

Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study.

BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. RESULTS: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. CONCLUSIONS: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors. © 2016 International Parkinson and Movement Disorder Society.

Off the wall: incidental paraspinal and pelvic muscle pathology on abdominopelvic imaging.

As the use of cross-sectional abdominal and pelvic imaging has increased exponentially in the past several decades, incidental musculoskeletal findings have become commonplace. These are often unrelated to the indication for the examination and are frequently referred to as the "radiologist's blind spot" on these studies. The differential diagnosis for abnormalities of the paraspinal and pelvic musculature is, in many cases, quite different from the anterior abdominal wall muscles. Furthermore, due to their relatively deep location, pathology involving the former muscle groups is more likely to be clinically occult, often presenting only incidentally when the patient undergoes cross-sectional imaging. Effective treatment of diseases of these muscles is dependent on adherence to a diverse set of diagnostic and treatment algorithms. The purpose of this review article is to familiarize the radiologist with the unique pathology of these often-overlooked muscles of the abdomen and pelvis.

Structural variations in articular cartilage matrix are associated with early-onset osteoarthritis in the spondyloepiphyseal dysplasia congenita (sedc) mouse.

Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+) mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA). We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc) mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA. Mutant sedc/sedc, and control (+/+) cartilages were compared at two, six and nine months of age. Tissues were fixed, decalcified, processed to paraffin sections, and stained with hematoxylin/eosin and safranin O/fast green. Samples were analyzed under the light microscope and the modified Mankin and OARSI scoring system was used to quantify the OA-like changes. Knees were stained with 1C10 antibody to detect the presence and distribution of type II collagen. Electron microscopy was used to study chondrocyte morphology and collagen fibril diameter. Compared with controls, mutant articular cartilage displayed decreased fibril diameter concomitant with increases in size of the pericellular space, Mankin and OARSI scores, cartilage thickness, chondrocyte clustering, proteoglycan staining and horizontal fissuring. In conclusion, homozygous sedc mice are subject to early-onset knee OA. We conclude that collagen in the mutant's articular cartilage (both heterozygote and homozygote) fails to provide the normal meshwork required for matrix integrity and overall cartilage stability.

Anti-inflammatory drug use and progressive supranuclear palsy.

BACKGROUND: Anti-inflammatory drug use, particularly ibuprofen, has been associated with a lower risk of Parkinson's disease. Microglial activation and inflammatory cytokine expression have been shown to be pathological features of progressive supranuclear palsy. We examined the association between NSAID use and risk of PSP, disease severity and age at onset. METHODS: The ENGENE-PSP multicenter case-control study recruited incident PSP cases who met the NINDS-PSP Society diagnostic criteria and age-, sex- and race-matched controls primarily from the same geographical areas. All subjects underwent standardized interviews to obtain data on demographics, residential history, medication history and lifetime occupational history. NSAID use was specifically queried by telephone interview using a standardized questionnaire. RESULTS: Information was obtained on anti-inflammatory drug exposure in 276 cases and 278 controls. No association was found between NSAID exposure and risk of PSP, age at onset or rate of change of UPDRS motor subscale, PSP Rating Scale or Mattis Dementia Rating Scale scores. This lack of association persisted when NSAID exposure was measured considering any NSAIDs, ibuprofen only, ASA only or non-ibuprofen, non-aspirin NSAIDs. CONCLUSIONS: These results do not suggest an important association between NSAID use and PSP occurrence or expression. Despite the large size of our study, confidence intervals were wide. To rule out small associations, very large sample sizes will be required.

Impact of lung cancer screening results on smoking cessation.

BACKGROUND: Lung cancer screening programs may provide opportunities to reduce smoking rates among participants. This study evaluates the impact of lung cancer screening results on smoking cessation. METHODS: Data from Lung Screening Study participants in the National Lung Screening Trial (NLST; 2002-2009) were used to prepare multivariable longitudinal regression models predicting annual smoking cessation in those who were current smokers at study entry (n = 15489, excluding those developing lung cancer in follow-up). The associations of lung cancer screening results on smoking cessation over the trial period were analyzed. All hypothesis testing used two sided P values. RESULTS: In adjusted analyses, smoking cessation was strongly associated with the amount of abnormality observed in the previous year's screening (P < .0001). Compared with those with a normal screen, individuals were less likely to be smokers if their previous year's screen had a major abnormality that was not suspicious for lung cancer (odds ratio [OR] = 0.811; 95% confidence interval [CI] = 0.722 to 0.912; P < .001), was suspicious for lung cancer but stable from previous screens (OR = 0.785; 95% CI = 0.706 to 0.872; P < .001), or was suspicious for lung cancer and was new or changed from the previous screen (OR = 0.663; 95% CI = 0.607 to 0.724; P < .001). Differences in smoking prevalence were present up to 5 years after the last screen. CONCLUSIONS: Smoking cessation is statistically significantly associated with screen-detected abnormality. Integration of effective smoking cessation programs within screening programs should lead to further reduction in smoking-related morbidity and mortality.