Arthroscopic Diagnosis of Occult Posterolateral Meniscocapsular Separations: Another Hidden Lesion.

PURPOSE: The purpose of this study was to describe the surgical findings and clinical outcomes in a series of patients with occult posterolateral meniscocapsular separations diagnosed arthroscopically after a negative magnetic resonance imaging (MRI) scan. METHODS: A retrospective analysis of prospectively collected data of consecutive patients who underwent surgical arthroscopy with repair of an occult posterolateral meniscocapsular separation by 2 fellowship-trained orthopaedic sports medicine surgeons at a single institution was performed. All lesions were identified arthroscopically in the posterolateral aspect of the lateral compartment as a distinct pathologic separation between the posterolateral capsule and adjacent meniscal tissue with increased excursion on probing. Clinical examination notes, MRI scans, and operative reports were reviewed. Patient-reported outcome measures were assessed via patient questionnaire. RESULTS: A total of 6 patients were included for analysis. MRI evaluation of the lateral meniscus was unrevealing in 4 patients, suggesting a possible tear of the body of the lateral meniscus in one patient and demonstrating a parameniscal cyst abutting the anterior root of the lateral meniscus in another patient. Arthroscopic examination revealed meniscocapsular separations of the posterolateral meniscus in all 6 knees, with 2 knees demonstrating concomitant bucket-handle meniscus tears. Patient-reported outcomes were determined for 67% of study patients. The average reported International Knee Documentation Committee score was 63.8, the average Knee Outcome Survey Activities of Daily Living Scale score was reported as 63, the 12-Item Short Form Survey (SF-12) Physical score averaged 46.8 with an average SF-12 Mental score of 59.9. CONCLUSIONS: The diagnosis of occult posterolateral meniscocapsular separations (MCS) could be missed on advanced imaging, such as MRI, so arthroscopic diagnosis may be required. This study indicates that arthroscopic diagnosis and repair of occult posterolateral MCS results in good functional and clinical outcomes. LEVEL OF EVIDENCE: IV, therapeutic case series.

CT Attenuation and Cross-sectional-area Index of the Pectoralis Are Associated With Prognosis in Sarcoma Patients.

BACKGROUND/AIM: To identify prognostic imaging biomarkers from staging chest computed tomography (CT) in patients with sarcomas. PATIENTS AND METHODS: CT scans for baseline staging, and surveillance 1-year CT scans in patients newly diagnosed with sarcoma were evaluated. Pectoralis muscle area (PMA), pectoralis muscle index (PMI) and pectoralis CT attenuation density (PMT) were measured. Cox proportional-hazard models were used to determine the association with progression-free survival (PFS) and overall survival (OS). RESULTS: There were 147 patients (53.1% male) who were followed for a median 1,414 days (range=219-4851 days). Approximately 47.6% (70/147) of patients progressed and 29.9% (44/147) died. Multivariable Cox-proportional hazards models adjusting for gender, tumor grade and chemotherapy treatment showed that a higher baseline PMT and baseline PMI were associated with increased OS. CONCLUSION: Higher baseline PMI and PMT are associated with increased overall survival in patients with sarcoma.

Osteosarcoma Mimicking Tenosynovial Giant Cell Tumor of the Hip in a Pediatric Patient: A Case Report.

CASE: A 17-year-old boy presented to the clinic complaining of right hip pain after soccer participation. Clinical findings and imaging studies led to the diagnoses of femoroacetabular impingement and diffuse tenosynovial giant cell tumor (TGCT). Comprehensive arthroscopic management and biopsy revealed a diagnosis of osteosarcoma. The patient subsequently underwent chemotherapy, surgical resection, and reconstruction. CONCLUSION: Osteosarcoma of the proximal femur may mimic TGCT on imaging studies because osteosarcoma may show changes suggestive of inflammation. We recommend heightened clinical awareness and a comprehensive differential workup in the management of presumed TGCT about the hip in the pediatric patient population.

A Rare Incident of Intraarticular Fibromatosis of the Knee: A Case Report.

CASE: Our patient is a 34-year-old male aHthlete who presented for consultation after left knee discomfort and pressure for greater than 2 years. Advanced imaging revealed a nonspecific intraarticular suprapatellar lesion with subsequent ultrasound-guided core biopsy demonstrating a spindle cell proliferation consistent with superficial fibromatosis. Thus, the patient underwent an open en bloc surgical resection by a fellowship-trained orthopaedic oncologist. CONCLUSION: As the first reported case of intraarticular fibromatosis of the knee, this case highlights the importance of a thoughtful approach to the management of nonspecific intraarticular lesions through a comprehensive and collaborative strategy to decrease patient morbidity and optimize outcomes.

Ultrasound guided aspiration of massive periarticular calcinosis in patient with scleroderma.

Massive periarticular calcinosis is poorly understood process arising either primarily (tumoral calcinosis) or secondary to underlying medical conditions, including connective tissue disease, soft tissue sarcoma, and metabolic dysregulation. The calcific deposits can cause functional limitation, skin ulceration, and cosmetic deformity. Treatment of the calcific deposits depends on the underlying cause but can be problematic with resistance to surgical and non-surgical treatments. Here, we introduce a case of tumoral calcinosis secondary to scleroderma treated with ultrasound guided aspiration.

Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer.

OBJECTIVES: Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTVWB) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTVWB to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTVWB, MTVWB may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTVWB in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. METHODS: We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTVWB, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTVWB. The optimal MTVWB cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. RESULTS: The optimal MTVWB cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTVWB (below 29.2 mL) and the stage IIIA patients with high MTVWB (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTVWB stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTVWB stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTVWB was observed in a large range of cutoff values from 15 to 55 mL in stage IIIA patients. CONCLUSIONS: Using MTVWB cutoff points ranging from 15 to 55 mL with an optimal value of 29.2 mL, stage IIIA NSCLC may be effectively stratified into subgroups with no significant survival difference from stages IIB or IIIB NSCLC. This may result in more accurate survival estimation and more appropriate risk adapted treatment selection in stage IIIA NSCLC.

Targeting recruitment of disruptor of telomeric silencing 1-like (DOT1L): characterizing the interactions between DOT1L and mixed lineage leukemia (MLL) fusion proteins.

The MLL fusion proteins, AF9 and ENL, activate target genes in part via recruitment of the histone methyltransferase DOT1L (disruptor of telomeric silencing 1-like). Here we report biochemical, biophysical, and functional characterization of the interaction between DOT1L and MLL fusion proteins, AF9/ENL. The AF9/ENL-binding site in human DOT1L was mapped, and the interaction site was identified to a 10-amino acid region (DOT1L865-874). This region is highly conserved in DOT1L from a variety of species. Alanine scanning mutagenesis analysis shows that four conserved hydrophobic residues from the identified binding motif are essential for the interactions with AF9/ENL. Binding studies demonstrate that the entire intact C-terminal domain of AF9/ENL is required for optimal interaction with DOT1L. Functional studies show that the mapped AF9/ENL interacting site is essential for immortalization by MLL-AF9, indicating that DOT1L interaction with MLL-AF9 and its recruitment are required for transformation by MLL-AF9. These results strongly suggest that disruption of interaction between DOT1L and AF9/ENL is a promising therapeutic strategy with potentially fewer adverse effects than enzymatic inhibition of DOT1L for MLL fusion protein-associated leukemia.

Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation.

Disruptor of telomeric silencing 1-like (Dot1l) is a histone 3 lysine 79 methyltransferase. Studies of constitutive Dot1l knockout mice show that Dot1l is essential for embryonic development and prenatal hematopoiesis. DOT1L also interacts with translocation partners of Mixed Lineage Leukemia (MLL) gene, which is commonly translocated in human leukemia. However, the requirement of Dot1l in postnatal hematopoiesis and leukemogenesis of MLL translocation proteins has not been conclusively shown. With a conditional Dot1l knockout mouse model, we examined the consequences of Dot1l loss in postnatal hematopoiesis and MLL translocation leukemia. Deletion of Dot1l led to pancytopenia and failure of hematopoietic homeostasis, and Dot1l-deficient cells minimally reconstituted recipient bone marrow in competitive transplantation experiments. In addition, MLL-AF9 cells required Dot1l for oncogenic transformation, whereas cells with other leukemic oncogenes, such as Hoxa9/Meis1 and E2A-HLF, did not. These findings illustrate a crucial role of Dot1l in normal hematopoiesis and leukemogenesis of specific oncogenes.

MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia.

OBJECTIVE: The aim of this study was to better understand how mixed lineage leukemia (MLL) fusion proteins deregulate the expression of genes critical for leukemia. MATERIALS AND METHODS: The transforming domain of one of the most common MLL fusion partners, AF9, was immunopurified after expression in myeloblastic M1 cells, and associating proteins were identified by mass spectrometric analysis. Chromatin immunoprecipitation followed by quantitative polymerase chain reaction was used to determine how binding of associating proteins compare across Hoxa9 and Meis1 in cell lines with and without MLL fusion proteins and how binding is altered during gene down-regulation and differentiation. RESULTS: Consistent with earlier purifications of ENL and AF4 from 293 cells, the 90 amino acid C-terminal domain of AF9 associates with many other MLL translocation partners including Enl, Af4, Laf4, Af5q31, Ell, and Af10. This complex, termed elongation assisting proteins (EAPs), also contains the RNA polymerase II C-terminal domain kinase Cdk9/Cyclin T1/T2 (pTEFb) and the histone H3 lysine 79 methyltransferase Dot1L. Myeloid cells transformed by MLL fusions show higher levels and a broader distribution of EAP components at genes critical for leukemia. Inhibition of EAP components pTEFb and Dot1l show that both contribute significantly to activation of Hoxa9 and Meis1 expression. EAP is dynamically associated with the Hoxa9 and Meis1 loci in hematopoietic cells and rapidly dissociates during induction of differentiation. In the presence of MLL fusion proteins, its dissociation is prevented. CONCLUSIONS: The findings suggest that MLL fusion proteins deregulate genes critical for leukemia by excessive recruitment and impaired dissociation of EAP from target loci.