Faculty Bibliography

Chondroblastoma is currently classified as a benign neoplasm; however, chondroblastoma and chondroblastoma-like osteosarcoma have morphologic overlap, raising the possibility that some tumors diagnosed as chondroblastoma-like osteosarcoma might actually represent malignant chondroblastoma. The H3F3B K36M point mutation, which has not been reported in osteosarcoma, is identified in 95% of chondroblastomas and is reliably detectable by immunohistochemistry (IHC). We reviewed 11 tumors diagnosed as atypical chondroblastoma, malignant chondroblastoma, or chondroblastoma-like osteosarcoma (median follow-up: 8.8 years; range: 4 months-26.4 years). Seven chondroblastomas with cytologic atypia and permeative growth were designated "malignant chondroblastoma"; six were H3K36M-positive by IHC. Relative to conventional chondroblastoma, malignant chondroblastoma occurred in older individuals (median: 52 years; range: 29-57 years) and arose at unusual sites. Three of four tumors with long-term follow-up recurred, and one patient died of widespread metastases. One was found to have chromosomal copy number alter4ations and a SETD2 mutation in addition to H3F3B K36M. The four remaining tumors were classified as chondroblastoma-like osteosarcoma. Chondroblastoma-like osteosarcoma occurred in younger patients (median: 21 years; range: 19-40 years) than malignant chondroblastoma. In contrast to malignant chondroblastoma, all had regions of malignant cells forming bone. Two of three patients with long-term follow-up developed recurrences, and two died of disease, one with widespread metastases. No mutations in H3F3A/H3F3B were detected by Sanger sequencing. While malignant chondroblastoma and chondroblastoma-like osteosarcoma show significant morphologic overlap, they have distinct clinical presentations and genetic findings. When considering this challenging differential diagnosis, IHC using histone H3 mutation-specific antibodies is a critical diagnostic adjunct.

PURPOSE/OBJECTIVE:Ischiofemoral impingement (IFI) is associated with abnormalities of the quadratus femoris muscle and narrowing of the ischiofemoral (IF) and quadratus femoris (QF) spaces. The hip abductors play an important role in pelvic stability and abductor tears might play a role in the pathophysiology of IFI. The purpose of our study was to assess the association between hip abductor tears and IFI on MRI. MATERIALS AND METHODS/METHODS:The study was IRB approved and HIPAA compliant. Inclusion criteria were MRI findings of IFI (narrowing of the IF space ≤ 15 mm or QF space ≤ 10 mm with associated ipsilateral quadratus femoris edema or fatty infiltration/atrophy). Two MSK radiologists assessed hip/pelvic MRIs and integrity of the tensor fascia lata, gluteus medius, and minimus tendons. IFI and control groups were compared with a two-tailed Student t test or chi-squared test. RESULTS:We identified 140 patients with MRI findings of IFI (mean age 56 ± 13 years, 130 f, 10 m) and 140 controls of similar age and sex. Patients with IFI had a higher prevalence of gluteus medius/minimus partial tears (37 vs 21, p = 0.02) and full-thickness tears (24 vs 21, p = 0.03). Patients with IFI had a higher prevalence and higher grade of gluteal muscle atrophy compared with controls (p < 0.03). There were no tears of the tensor fascia lata in either group. CONCLUSION/CONCLUSIONS:Patients with IFI had a higher prevalence of abductor tears and abductor muscle atrophy compared with matched controls. This suggests that abductor tears might play a role in the pathophysiology of IFI.

Data are conflicting regarding the impact of weight loss on mood and anxiety in adolescent and young adult females with moderate to severe obesity (OB), who are at increased risk for mood dysfunction compared with normal-weight females (NW). We examined depressive and anxiety symptoms in 94 females 13-21 years old: 39 in the NW group (body mass index [BMI]: 5^th -85^th percentiles) and 55 in the OB group (BMI >40 kg/m² or >35 kg/m² with comorbidities). Fifteen participants in the OB group who underwent bariatric surgery (gastric bypass or sleeve gastrectomy) and 15 getting routine care were re-assessed after 6 months. The Beck Depression Inventory-II (BDI-II) and State-Trait Anxiety Inventory (STAI) assessed depressive and anxiety symptoms, respectively. The OB group had higher BDI-II and STAI T-scores (P < .0001), a higher prevalence of clinical depression and anxiety (P < .001), and reported greater suicidal ideation (P = .02) vs the NW group. The bariatric surgery and non-surgical groups did not differ for changes in BDI-II and STAI T-Scores and suicidality over 6-month follow-up, despite greater weight loss in the former. Depressive and anxiety symptoms and suicidality were more frequently observed in the OB vs NW group. These symptoms did not improve following bariatric surgery despite significant weight loss, underscoring the need to investigate determinants of emergence and resolution of these symptoms in the OB group.

BACKGROUND/OBJECTIVE:Less muscle mass has been associated with greater insulin resistance, but whether the association is independent of deleterious adipose depots in young adults with overweight/obesity who are at high risk for type 2 diabetes (T2DM) but are otherwise metabolically healthy is not known. The objective of this study was to determine whether muscle mass is independently associated with insulin sensitivity (IS) in young adults with overweight/obesity. SUBJECTS/METHODS:and metabolically healthy without T2DM. Primary independent variable: percent ideal appendicular lean mass (ALM) calculated as measured ALM divided by predicted ALM for age, weight, and height, calculated using validated NHANES data-based equation. Primary dependent variable: IS by Matsuda index. RESULTS:(mean ± SD). Individuals in the highest % ideal ALM tertile had mean IS 45% higher than the lowest tertile [6.94 ± 0.85 vs 4.80 ± 0.56 (mean ± SEM), p = 0.008] (sex interaction p = 0.003). Men in the highest % ideal ALM tertile had mean IS twice the lowest tertile (5.47 ± 0.68 vs 2.68 ± 0.34, p = 0.001), which remained significant controlling for visceral/subcutaneous and intermuscular adipose tissue, and intramyocellular and intrahepatic lipids (p = 0.03). The association was not significant in women. CONCLUSIONS:Muscle mass is associated with IS independent of detrimental adipose depots in young men with overweight/obesity, at risk for T2DM but currently metabolically healthy. Muscle mass relative to sex, age, weight, and height-specific norms may be used to ascertain individual T2DM risk associated with low muscle mass.

BACKGROUND:African Americans (AA) have more favorable bone density and microarchitecture compared to Whites (W), which may explain their observed lower fracture rates. Obesity has deleterious effects on bone microarchitecture and strength estimates and is associated with an increase in fracture risk. Adolescence and young adulthood are periods of active bone accrual and also periods characterized by an increasing prevalence of obesity. The effect of obesity on the relationship between race and bone parameters remains unclear, particularly in youth. OBJECTIVE:To assess differences in BMD, bone microarchitecture and strength estimates in AA and W adolescents and young adults with moderate to severe obesity. We hypothesized that racial differences in bone endpoints in lean youth would also be noted in youth with moderate to severe obesity. METHODS:who underwent dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT), extended cortical analysis (ECA) and micro-finite element analysis (FEA) to obtain measures of volumetric bone mineral density (vBMD), bone geometry, microarchitecture, and strength estimates at the distal radius and tibia. RESULTS:We found no differences between AA and W for total fat and lean mass, and areal BMD Z-scores (p > 0.05 for all). At the distal radius, no significant differences were detected in vBMD, bone geometry or microarchitecture (p > 0.05 for all); however, stiffness and failure load were higher in the AA group (p = 0.031 and 0.047 respectively). At the distal tibia, cortical vBMD was higher in AA vs. W (p = 0.012), while trabecular number was higher and trabecular separation lower in W vs. AA (p ≤ 0.028). Stiffness and failure load trended higher in AA vs. W (p = 0.052 and p = 0.048, respectively). Groups did not differ for any other bone parameter (p > 0.05). CONCLUSION:Racial differences in bone endpoints appear to be less marked in those with moderate to severe obesity, suggesting that effects of obesity may blunt the effect of race on bone endpoints.

Dedifferentiated chordoma is a rare chordoma subtype characterized by a high-grade sarcoma juxtaposed to conventional chordoma. We identified a series of dedifferentiated chordomas, reviewed clinicopathologic features, performed next-generation sequencing in select cases, and analyzed all related English-language publications. Our series included 7 men and 3 women (age 15 to 80 y [median: 54 y]; <1% of >1000 chordomas surveyed). The tumor (2.8 to 24.5 cm [median: 5.8 cm] in size) presented de novo or as recurrence (including postradiotherapy) in sacrum (n=5), skull base (n=2), lumbar spine (n=1), thoracic/mediastinum (n=1), and lung (n=1; as metastasis). Histologically, the dedifferentiated component (3% to 95% [median: 60%]) was pleomorphic-to-fibrosarcomatous, juxtaposed to conventional (n=8) or chondroid (n=2) component. By immunohistochemistry, the conventional/chondroid component consistently expressed cytokeratin and brachyury, whereas the dedifferentiated component showed loss of both. We identified a sacral conventional chordoma with INI1 loss, with one of the lung metastases showing biphasic histology with loss of cytokeratin and brachyury in the dedifferentiated component. Sequencing identified tumor suppressor mutations in 4 tumors, including TP53 mutations in the dedifferentiated component in 3 tumors. Of 7 patients with follow-up, 6 developed metastases; 4 died at 15 to 99 months (median: 24 mo) after dedifferentiated chordoma diagnosis. Collectively, of 87 dedifferentiated chordoma patients described in 1913-2020 (including 10 herein), the median overall survival was 20 months. In summary, dedifferentiated chordoma involves diverse sites and presents de novo, postradiotherapy, or as recurrence/metastasis months-to-years after initial diagnosis. The dedifferentiated component shows loss of brachyury and cytokeratin staining and harbors recurrent TP53 mutations, implicating tumor suppressor dysregulation in chordoma dedifferentiation.

PURPOSE/OBJECTIVE:To compare the pathology results of CT-guided and blind bone marrow aspirations and biopsies. METHODS:Ninety-eight consecutive CT-guided biopsies and 98 age- and gender-matched blind (non-CT-guided) posterior iliac crest bone marrow aspirations and biopsies performed in 2017 were reviewed for adequacy of core biopsies and aspirate smears. CT procedure images and CT abdomen/pelvis images were reviewed to evaluate anatomic features of the posterior ilium and soft tissues. Statistical analysis was performed using a T test, Fisher exact test, and Kruskal-Wallis test. RESULTS:There was no significant difference in the age and gender of the two groups (p > 0.05). However, the CT-guided group had a higher BMI (p = 0.0049) and posterior soft tissue thickness (p = 0.0016). More CT-guided biopsy samples (CT 93 (95%); blind 77 (79%); p = 0.0006) and aspirate smears (CT 90 (92%); blind 78 (80%); p = 0.042) were categorized as adequate. The CT-guided group had longer core lengths (CT 1.4 ± 0.6 (range 0.3-3.5) cm; blind 1.0 ± 0.60 (range 0-2.6) cm; p = 0.0001). Overall, 131/164 (80%) of the cases had at least one of the described features (slanted posterior ilium (angle > 30°), 30%; rounded posterior ilium, 20%; thick posterior ilium cortex, 13%; focal lesion in posterior ilium, 12%; prior procedure in posterior ilium, 5%; posterior soft tissue thickness > 3 cm, 40%). CONCLUSION/CONCLUSIONS:CT-guided bone marrow procedures were more likely to result in both adequate aspirate smears and biopsy samples and longer core lengths when compared with blind procedures.

PURPOSE/OBJECTIVE:To determine (i) whether intra-articular gadolinium from MR arthrography (MRA) results in gadolinium deposition in the brain and (ii) whether there is a correlation between intra-articular gadolinium dose and intracranial gadolinium deposition. MATERIALS AND METHODS/METHODS:This retrospective study was institutional review board (IRB) approved and HIPAA compliant. The study group included consecutive adult patients who had undergone MRA of the hip or shoulder and subsequent MRI of the brain. None of the patients had a history of intravenous gadolinium exposure. A control group of patients of similar age and sex who were never exposed to gadolinium and had brain MRIs available was included. Signal intensities (SI) of four brain regions: pons, dentate nuclei (DN), globus pallidi (GP), and thalamus (Thal) normalized to cerebrospinal fluid (CSF) and expressed in SI ratios were measured on T1-weighted non-contrast MR images. Groups were compared using the student's t test. Linear correlation analysis of gadolinium dose and brain SI ratios was performed, and Pearson correlation coefficients (r) are reported. RESULTS:We identified 109 patients (mean age 44 ± 14 years, 54% men) who had undergone MRA and 149 controls of similar age and sex distribution. There was no significant difference in mean SI ratios of the brain regions between patients and controls: pons/CSF (p = 0.7), DN/CSF (p = 0.4), GP/CSF (p > 0.99), Thal/CSF (p = 0.3). Within the MRA group, gadolinium dose was not associated with SI ratios (p > 0.2). CONCLUSION/CONCLUSIONS:Our study found no MR evidence of intracranial gadolinium deposition following MRA. In addition, there was no association between intra-articular gadolinium dose and SI ratios in commonly affected regions of the brain.

Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.