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.

Overall survival and tumor recurrence after surgical resection for primary malignant chest wall tumors: a single-center, single-surgeon experience.

BACKGROUND AND OBJECTIVES: Malignant primary chest wall tumors (PCWTs) comprise a rare group of thoracic tumors with unique anatomical considerations, and experience with wide surgical resection is limited to specialty referral centers and specific diagnoses. We investigated the tumor recurrence and overall survival (OS) for patients with a variety of PCWTs diagnoses at our institution. METHODS: From 1991 to 2010, patients with malignant PCWT undergoing wide surgical resection for curative intent under a single surgeon were reviewed. Diagnosis and grade (if applicable) of surgical pathology, along with patient demographics, neoadjuvant chemotherapy or radiation therapy, and outcomes (complications, recurrence, and OS) at follow-up were analyzed. RESULTS: One hundred fifteen patients were included in the study. The most common tumor diagnoses included pleomorphic sarcoma and liposarcoma. Negative margins were achieved in 70 (74%) of cases. Postoperative complications were reported in 21 (20%) cases. The 5-year survival rate was 54%, while the 10-year survival rate was 29%. The local and distant recurrence rates were 50% and 38%, respectively. OS was significantly less in patients with any recurrence ( p < 0.001) but not significantly different between pathology grades ( p = 0.28). CONCLUSIONS: Wide resection for malignant PCWT is feasible when undertaken for a heterogenous group of diagnoses.

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.

Primary intraosseous schwannoma in tibial epiphysis with unique immunohistochemical phenotype: a case report.

Schwannoma is a benign peripheral nerve sheath neoplasm of soft tissue that consistently demonstrates immunohistochemical staining for S100 protein. Intraosseous location of schwannoma is very uncommon. We report the first case of an intraosseous schwannoma located in the epiphysis of tibia in an adult patient. Radiologically, it mimicked a primary bone tumor and despite benign histological appearance, the tumor eroded cortical bone. Morphologically on routine stains and electron microscopy it has features of a schwannoma. But by immunohistochemistry, the tumor was positive for both desmin and S100 protein in the same region.

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.

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.

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.

Sox9 expression is not limited to chondroid neoplasms: variable occurrence in other soft tissue and bone tumors with frequent expression by synovial sarcomas.

The transcription factor Sox9 is known to play a crucial role in normal chondrogenesis, and antibodies against Sox9 have been proposed as a diagnostic tool for neoplasms with chondroid differentiation. However, the pattern of Sox9 immunohistochemical expression by other bone and soft tissue neoplasms, as well as its diagnostic specificity, remain unexplored. The authors have performed immunohistochemistry with antibodies against Sox9 in 106 chondroid and nonchondroid bone and soft tissue neoplasms. Moderate to intense Sox9 nuclear staining was observed in 14/20 chondrosarcomas (70%), and in 24/81 (29.6%) cases from a multitumor tissue microarray, which included 16/18 synovial sarcomas, 4/15 osteosarcomas, 2/5 peripheral primitive neuroectodermal tumor (PNET)/Ewing sarcomas, 1/1 mesenchymal chondrosarcoma, and 1/1 chondroblastoma. The results suggest that Sox9 usefulness in the diagnosis of chondroid tumors may be limited because of low sensitivity and specificity. The finding of Sox9 expression by 88.9% of synovial sarcomas represents a novel and striking observation, which deserves further investigation.

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.

Comparison of allelic losses in chondroblastoma and primary chondrosarcoma of bone and correlation with fluorescence in situ hybridization analysis.

Chondroblastoma (CBL) is a benign neoplasm of bone for which the genomic characteristics remain unclear. We compared the status of allelic losses of CBL with that seen in a set of chondrosarcomas (CS) to determine whether differences in their natural history and behavior are also reflected genetically. Eleven cases of CBL and 10 cases of CS of different grades were included. Tumors were subjected to microdissection and polymerase chain reaction using 17 markers located near genes on chromosomes 5, 9, 11, 13, 17, and 19. The selected chromosomes are known to be involved in several mesenchymal neoplasms. Fluorescence in situ hybridization was also performed on tumors displaying allelic losses, with dual-color probes for 9p, 17p, and 13q. Fractional allelic losses per gene ranged from 18.2% to 63.7% in CBLs and from 28.6% to 66.7% in CSs. Loss of heterozygosity (LOH) of 5q, 9p, 11p, 13q, and 19q occurred in both CBLs and CSs. Loss of heterozygosity of 17p (p53 locus) occurred in 7 of 11 CBLs and in only 1 case of recurrent CS. The pattern of allelic loss was similar in low-grade CSs and CBLs. Loci with LOH in both tumor types suggest possible involvement of the genes p53, RB1, CDKN2/p16, ERC, and XRCC in tumorigenesis. Overall correlation between LOH and fluorescence in situ hybridization results was 90% with 17p13, 80% with 9p, and 60% with 13q. The role of p53 in CBL is uncertain; however, given the benign behavior of this tumor, it is probably unrelated to tumor progression.

A system for the surgical staging of musculoskeletal sarcoma. 1980.

Historically, an adequate surgical procedure has been the most effective means of treating the majority of primary musculoskeletal sarcomas, and amputation has figured prominently in the surgical armamentarium. 4, 7, 9, 19, 21, 29, 41 The recent evidence that certain chemotherapeutic agents may have significant anti-sarcoma activity 2, 15, 17, 38 and coincident technical advances in irradiation therapy, radiographic localization, and reconstructive surgery have fostered enthusiastic interest in extremity-saving treatments. Almost all such treatments emphasize limb salvage as an alternative to amputation and are usually performed under a protective cloak of adjunctive chemotherapy, irradiation or immunoactive agents. 20, 23, 24, 30, 37, 39 Since neither chemotherapy nor irradiation therapy alone has been shown to assure long-term local control of bulk disease, surgical intervention remains an essential step in the overall management of musculoskeletal sarcomas. 3, 9, 17, 18, 29 Questions concerning the magnitude and timing of the surgical procedure are as unanswered as those relating to the most appropriate use of the adjuncts themselves. Increasingly, the surgeon and his patient are confronted with a bewildering array of therapeutic options, the long-term outcomes of which are unknown. These relatively rare sarcomas increasingly are distributed among a variety of treatment protocols in which multiple parameters differ. This trend necessitates interinstitutional cooperation if sufficient numbers of patients are to be available for the timely evaluation of treatments in clinical use. Such cooperation and even effective interinstitutional communication are seriously hampered by the lack of uniform language, so that meaningful comparison of treatments is currently impossible. Prime factors include the lack of a consistent definition of the surgery performed and a serviceable surgical staging system encompassing bone and soft tissue. Standard terminology will assure that like and unlike treatments are appropriately compared. Although an effective staging system should serve all members of the multidisciplinary team, the biologic behavior of musculoskeletal sarcomas suggests that the most useful staging system will articulate with the surgical procedure.