Novel MEAF6-SUZ12 fusion in ossifying fibromyxoid tumor with unusual features.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation that has the capacity for local recurrence and metastasis. Many OFMTs, including typical, atypical, and malignant tumors, have demonstrated recurrent gene fusions. The fusion partners reported to date share a common core function in that they play either a direct or indirect role in processes influencing histone modification. Herein, we report an OFMT with unusual morphology and non-specific immunoprofile harboring a novel MEAF6-SUZ12 fusion. A 34-year-old male presented with a slowly growing mass in the right antecubital fossa. Excision demonstrated a 6.9 cm partially encapsulated, tan-white, lobulated, and calcified lesion. Microscopic evaluation demonstrated cytologically bland spindle to ovoid cells arranged in a haphazard manner within a fibromyxoid background containing dense collagen, often with sclerotic nodules, and randomly distributed ossification. The tumor cells were diffusely positive for CD34 while essentially negative for S100, desmin, MUC4, SOX10, AE1/3, SMA, and EMA. Next-generation sequencing studies (sarcoma gene fusion next-generation sequencing panel with subsequent Sanger confirmation) performed on formalin-fixed paraffin-embedded tissue detected a fusion product between MEAF6 exon 4 (NM_001270875) and SUZ12 exon 2 (NM_001321207.1). The proposed mechanism of pathogenesis in OFMT, namely epigenetic dysregulation, is reinforced by the fact that both of these partner genes are involved in histone modification.

What's Wrong With the Bone? An Overview of Metabolic and Neoplastic Bone Conditions.

The evaluation of any orthopaedic condition often begins with obtaining plain radiographs. Fortuitously, plain radiographs provide surgeons with direct information on the biologic activity and, therefore, the aggressiveness of any bone lesion. More advanced imaging modalities may fail to elucidate the problem and may even obscure the diagnosis. The accurate interpretation of the aggressiveness of a bone lesion on plain radiographs is the first step in establishing a differential diagnosis for any bone lesion and, often, may result in a correct diagnosis without the need for additional imaging studies. A thorough understanding of the radiographic classification of bone lesions will allow surgeons to accurately diagnose and manage metabolic bone disease, benign bone lesions, and malignant bone lesions.

Does combined open and arthroscopic synovectomy for diffuse PVNS of the knee improve recurrence rates?

BACKGROUND: Diffuse-type pigmented villonodular synovitis (PVNS) has a high local recurrence rate and as such can lead to erosive destruction of the involved joint. Multiple surgical modalities exist, but it is unknown which technique best minimizes local recurrence and surgical morbidity. QUESTIONS/PURPOSES: We compared recurrence rates, arthritis progression, and complications between arthroscopic and open modalities for diffuse PVNS of the knee. METHODS: We retrospectively identified 103 patients with PVNS treated between 1993 and 2011. Of these, 48 had diffuse-type PVNS of the knee treated by all-arthroscopic, open posterior with arthroscopic anterior, or open anterior and open posterior synovectomy. We recorded patient demographics, treatment profiles, recurrence rates, and arthritic progression. Minimum followup was 3 months (median, 40 months; range, 3-187 months). RESULTS: Recurrence rates were lower in the open/arthroscopic group compared with the arthroscopic or open/open groups: 9% versus 62% versus 64%, respectively. Arthritic progression occurred in 17% of the total study group with 8% going onto total knee arthroplasty within the followup period. We detected no difference between groups with regard to arthritic progression or progression to arthroplasty. The most common complication was hemarthrosis, which we drained in three patients (6% of the total study group), but there were no detectable differences between groups. CONCLUSION: Open posterior with arthroscopic anterior synovectomy is a viable, comprehensive approach to diffuse PVNS of the knee and provides both low recurrence rates and a low postoperative complication profile. Greater numbers of recurrences may be partially explained in the arthroscopic group by technical challenges associated with posterior arthroscopic synovectomy and in the open/open group by selection bias toward more aggressive disease. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Primary versus secondary distal femoral arthroplasty for treatment of total knee arthroplasty periprosthetic femur fractures.

Current methods of fixing periprosthetic fractures after total knee arthroplasty (TKA) are variable, and include open reduction and internal fixation (ORIF) via plating, retrograde nailing, or revision using standard revision TKA components or a distal femoral arthroplasty (DFA). The purpose of this study is to compare patients who failed plating techniques requiring subsequent revision to DFA to patients who underwent primary DFA. Of the 13 patients (9.2%) who failed primary ORIF, causes included nonunion (53.8%), infection (30.8%), loosening (7.7%), and refracture (7.7%). There were significantly more surgical procedures for ORIF revision to DFA compared to primary DFA. Complications for patients who underwent primary reconstruction with DFAs included extensor mechanism disruption (8.3%), infection (5.6%), and dislocation (2.8%). Primary reconstruction via ORIF is beneficial for preserving bone stock, but primary DFA may be preferred in osteopenic patients, or those at high risk for nonunion.

Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging.

Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0-2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon's clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28-83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.

Should Aggressive Surgical Local Control Be Attempted in All Patients with Metastatic or Pelvic Ewing's Sarcoma?

In previous reports, patients with Ewing's sarcoma received radiation therapy (XRT) for definitive local control because metastatic disease and pelvic location were thought to preclude aggressive local treatment. We sought to determine if single-site metastatic disease should be treated differently from multicentric-metastatic disease. We also wanted to reinvestigate the impact of XRT, pelvic location, and local recurrence on outcomes. Our results demonstrated a significant difference in overall survival (OS) between patients with either localized disease or a single-metastatic site and patients with multicentric-metastatic disease (P = 0.004). Local control was also found to be an independent predictor of outcomes as demonstrated by a significant difference in OS between those with and without local recurrence (P = 0.001). Axial and pelvic location did not predict a decreased OS. Based on these results, we concluded that pelvic location and the diagnosis of metastatic disease at diagnosis should not preclude aggressive local control, except in cases of multicentric-metastatic disease.

Preoperative screening/decolonization for Staphylococcus aureus to prevent orthopedic surgical site infection: prospective cohort study with 2-year follow-up.

We quantified surgical site infections (SSIs) after preoperative screening/selective decolonization before elective total joint arthroplasty (TJA) with 2-year follow-up and 2 controls. Concurrent controls (n = 2284) were patients of surgeons not participating in screening/decolonization. Preintervention controls (n = 741) were patients of participating surgeons who underwent TJA the previous year. Staphylococcus aureus nasal carriers (321/1285 [25%]) used intranasal mupirocin and chlorhexidine baths as outpatients. Staphylococcal SSIs occurred in no intervention patients (0/321) and 19 concurrent controls. If all SSIs occurred in carriers and 25% of controls were carriers, staphylococcal SSI rate would have been 3.3% in controls (19/571; P = .001). Overall SSI rate decreased from 2.7% (20/741) in preintervention controls to 1.2% (17/1440) in intervention patients (P = .009). Preoperative screening/selective decolonization was associated with fewer SSIs after elective TJA.

Outcomes of revision total knee arthroplasty after methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: The incidence of infection by methicillin-resistant Staphylococcus aureus (MRSA) in total knee arthroplasty (TKA) is becoming a more frequent concern, as increased morbidity following TKA has been reported for infections by resistant organisms. This study investigates whether MRSA infections are associated with decreased functional scores. QUESTIONS/PURPOSES: We therefore compared the functional scores, operative times, and rates of reinfection of revision TKA following MRSA infection versus other indications for revision. METHODS: We retrospectively reviewed charts of 101 patients (103 knees) who underwent mobile bearing TKA revision from January 2003 to September 2006, with a minimum clinical followup of 2 years in 45 knees (44%). We obtained the following indices: WOMAC, Activities of Daily Living Score (ADLS), SF-36, and Knee Society scores (KSS). Three groups of revisions were compared: MRSA infection (n = 6), non-MRSA infection (n = 9), and aseptic failure (n = 30). The three groups were similar in demographics and comorbidities. RESULTS: The MRSA (166 minutes) and non-MRSA groups (149 minutes) had longer operative times than the aseptic group (121 minutes). With numbers available, there were no differences in ROM, WOMAC, ADLS, KSS, and SF-36, with MRSA separate or combined with all infections. Infection recurrence between MRSA-infected knees and non-MRSA-infected knees was similar. CONCLUSIONS: While our study was underpowered to detect functional differences between MRSA-infected knees and non-MRSA-infected knees it does add data to the literature. Knees revised for infection have longer operative times and more frequent infection after revision. The reason for increased operative times is unclear. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Atypical Lipomatous Tumors: Does Our Inconsistent Terminology Have Patient Repercussions? Results of a Meta-Analysis.

OBJECTIVES: Misnaming low-grade lipomatous tumors poses a clinical and medicolegal challenge, potentially subjecting patients to expensive and unnecessary surgeries. The terms atypical lipomatous tumor (ALT) and "well-differentiated" liposarcoma (WDL) have been used interchangeably in pathology reports, scholarly works and consensus recommendations, creating vagaries between low-virulence extremity tumors and retroperitoneal disease with metastatic potential. METHODS: A systematic review was performed on all studies that reported on the local recurrence rate and metastasis of ALTs and WDLs in living human subjects. Local recurrence and metastases were compared using Fisher's Exact Test. RESULTS: In total, 20 studies evaluated ALTs (n=936), whereas 13 studied WDLs (n=626). Mean follow-up was 6.6±2.0 years (median, 7.0 y). No metastatic disease was observed among ALTs, whereas 15 patients with WDLs (2.7%, P<0.0001) had metastases. The local recurrence rate of ALTs was significantly lower than WDLs after both marginal (15.1%, 141/936 vs. 46.0%, 288/626, P<0.0001) and wide excisions (3.3%, 2/59 in ALT vs. 17.4%, 19/109, P=0.007). CONCLUSIONS: ALT should be reserved for extremity lesions meeting appropriate histopathologic criteria that represent nonmetastatic disease, reducing over-diagnosis, over-treatment, and patient risk.

Angiomyomatous hamartoma of a popliteal lymph node: an unusual cause of posterior knee pain.

Angiomyomatous hamartoma is a primary vascular tumor primarily found in the inguinal and femoral lymph nodes characterized by the replacement of nodal tissue by smooth muscle cells and fibrous tissue in sclerotic lymphatic stroma. There has been 1 report of an angiomyomatous hamartoma of a cervical lymph node, and this is the first reported case occurring in an extremity. We present a case of angiomyomatous hamartoma occurring in a single popliteal lymph node.

Pseudomyogenic hemangioendothelioma of skin, bone and soft tissue-a clinicopathological, immunohistochemical, and fluorescence in situ hybridization study.

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon neoplasm with propensity for local recurrence. The tumor mimics epithelioid hemangioendothelioma and epithelioid sarcoma, representing a possible diagnostic pitfall. We investigated the clinicopathological, immunohistochemical, and fluorescence in situ hybridization features of PHEs. Eight cases of PHE were retrieved from our pathology archives. The clinical and outcome information was available in 6 patients. In 6 cases, the tumors were located in the lower limb, whereas the upper limb was involved in 2 cases. Three patients had exclusively bone involvement, and 2 patients had cutaneous tumor only. The tumor was multifocal in 5 cases, of which 2 patients had simultaneous bone and soft tissue involvement. Immunohistochemical stains revealed all tumors to be positive for AE1/AE3 (8/8), ERG (7/7), and FLI-1 (7/7) with preserved INI1 (7/7) expression. Most of the tumors were variably positive for CD31 (7/8), CAM5.2 (2/3), and SMA (4/6). t(7;19)(q22;q13) fusion pattern was detected in 3 cases (5 tumors) with cutaneous and multifocal PHE. In 3 cases, a translocation pattern was detected in a few nuclei but did not meet our laboratory cutoff value. MYC amplification was not detected in any of the 5 cases examined, aiding in ruling out the possibility of angiosarcoma. Four patients underwent excision, and 2 with multifocal tumor required below-knee amputation. Six patients with outcome information were alive and free of disease after a median follow-up of 35 months. We conclude that ancillary techniques can be helpful in differentiating this unusual indolent tumor from potentially aggressive epithelioid hemangioendothelioma, epithelioid sarcoma, and epithelioid angiosarcoma. Long-term follow-up is warranted.

Does metastasectomy improve survival in skeletal melanoma?

UNLABELLED: Melanoma metastatic to bone carries a poor prognosis with overall median survival in the 4-6 months range. Others have published data that suggest resection of isolated visceral organ metastases improves survival. We conducted a retrospective analysis of 130 cases of stage IV melanoma with pathologically confirmed bony disease. We used Cox regression survival analysis to compare a group of patients who underwent wide resection of metastases with those who received other surgery or were treated nonoperatively. We also compared the three groups against matched historical stage IV melanoma controls to determine differences between expected and observed 1-year overall survival. Median overall survival for the nonoperative (N=80), intralesional (N=32), and resection (N=18) groups was 4.8, 5.1, and 11.8 months, respectively. Cox regression survival analysis confirmed the overall survival benefit resulting from wide resection (hazard ratio 0.53) after correcting for independent predictors of worse survival, such as pathologic spinal compression fracture (hazard ratio 1.68). The observed 1-year overall survival rate in the resection group was nearly double that of matched historical controls (50.0 vs. 24.8%). We present the largest known series of bony melanoma, along with data which suggest that overall survival may be improved in carefully selected patients where all known macroscopic disease can be resected. LEVEL OF EVIDENCE: level III.

Immunohistochemical analysis of expressions of RB1, CDK4, HSP90, cPLA2G4A, and CHMP2B is helpful in distinction between myxofibrosarcoma and myxoid liposarcoma.

The role and diagnostic efficacy of gene and protein products RB1, CDK4, CHMP2B, HSP90, and cPLA2G4A, all previously shown to be involved in tumor genesis and cell proliferation, were examined by immunohistochemical techniques in 32 cases of myxofibrosarcomas and 29 myxoid liposarcomas (all diagnosis had been confirmed by fluorescence in situ hybridization). HSP90 demonstrated strong nuclear and cytoplasmic positivity in all myxoid liposarcoma cases, while only 4 myxofibrosarcomas showed scattered HSP90 positivity. All but 4 cases of myxofibrosarcoma displayed strong positivity for cPLA2G4A, while only 2 myxoid liposarcoma cases were cPLA2G4A positive and both were CHMP2B negative. Overexpression of both cPLA2G4A and CHMP2B also suggested higher tumor grade. In conclusion, HSP90 and cPLA2G4A immunohistochemical stains are useful markers to distinguish myxofibrosarcoma from myxoid liposarcoma.

ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone.

Osteosarcoma (OS), chondrosarcoma (CSA), and Ewings sarcoma (ES) are the most common primary malignancies of bone, and are rare diseases. As with all sarcomas, the prognosis of these diseases ultimately depends on the presence of metastatic disease. Survival is therefore closely linked with the biology and metastatic potential of a particular bone tumor's cells. Here we describe a significant correlation of aldehyde dehydrogenase (ALDH) activity and the presence/absence of distant metastases in ten consecutive cases of human bone sarcomas. Additionally, cultured human CSA cells, which are historically chemo- and radio-resistant, may be sensitive to the ALDH inhibitor, disulfiram. While it is premature to draw broad conclusions from such a small series, the importance of ALDH activity and inhibition in the metastatic potential of primary bone sarcomas should be investigated further.

Inpatient procedures in elderly women: an analysis over time.

OBJECTIVES: To describe inpatient surgical and diagnostic/therapeutic procedures in women ≥65 years old and assess procedure trends over time. STUDY DESIGN: Procedure data for all women ≥65 years was collected using the National Hospital Discharge Survey, a federal dataset drawn from a representative sampling of U.S. inpatient hospitals which includes patient and hospital demographics and ICD-9-CM diagnosis and procedure codes for admissions from 1979 to 2006. MAIN OUTCOME MEASURES: Age-adjusted rates (AAR) per 1000 women were created using 1990 U.S. Census data to compare trends over time. RESULTS: Over 96 million procedures were performed in women age≥65 years from 1979 to 2006. Women age≥65 years constituted 17% of women with ≥1 inpatient procedure in 1979, rising to 32% in 2006. The most common surgical procedures were lower extremity joint replacement, open reduction internal fixation, and cholecystectomy. The most common concurrent diagnosis was femoral neck fracture. Women with femoral neck fracture were more likely to undergo open reduction internal fixation compared to joint replacement. AARs for ORIF fell from 4.3 to 3.2 (p=.02) from 1979 to 2006, while AARs for joint replacement increased from 0.2 to 3.4 (p≤.001, 1979-1988; p=.14, 1990-2006). CONCLUSIONS: The rate of women age≥65 years undergoing inpatient procedures has increased dramatically in the last 30 years. Hip fracture was the most common diagnosis for elderly women, highlighting the impact of osteoporosis and falls and the importance of prevention strategies and optimization of peri-operative care in this population. Further comparative study of hip fracture treatment strategies in this population is needed.

Malignant granular cell tumor of the ulnar nerve with novel cytogenetic and molecular genetic findings.

We report an unusual case of ulnar nerve-based malignant granular cell tumor characterized by gains of chromosome 10 and loss of P16 detected by conventional karyotyping and by fluorescence in situ hybridization, respectively, in a 74-year-old male. To our knowledge, these findings have never been reported previously in malignant granular cell tumors.

Chondromyxoid fibroma of rib with a novel chromosomal translocation: a report of four additional cases at unusual sites.

BACKGROUND: Chondromyxoid fibromas (CMFs) are rare benign chondroid/myxoid matrix-producing tumors that occur in metaphyses of long tubular bones, and very rarely in small bones of hands and feet. Flat bone involvement is even more uncommon. Prior cytogenetic analyses have identified complex abnormalities involving chromosome 6 in the majority of cases. METHODS: A search for CMF over an 8-year period (1999-2006) from the surgical pathology files of our institution yielded 16 cases. Four cases occurred in relatively unusual regions, three from the small bones of distal extremities and one from the rib. The rib lesion was submitted for routine cytogenetic analysis. RESULTS: Radiographic studies revealed that all four lesions were well-defined expansile radiolucent lesions which expanded the bony cortices with lobulated margins, sclerotic rim, septation, and no calcification. Morphologically, all four lesions showed typical features of CMF and had low proliferative index with Ki-67. Cytogenetic analysis on the rib lesion revealed a novel chromosomal translocation, t(1;5)(p13;p13). None of the four patients had a recurrence after a mean duration of follow-up of 24 months. CONCLUSION: CMF originating in unusual locations should be distinguished from chondrosarcomas, especially on small biopsies, and should be included in the differential diagnosis. As previously noted in the literature, the cells can be positive for actin but unlike conventional chondroid neoplasms can be negative for S-100. To our knowledge, this is the first report describing a novel chromosomal translocation, t(1;5)(p13;p13) in CMF.