Joel L. Mayerson

20q11.1 amplification in giant‐cell tumor of bone: Array CGH, FISH, and association with outcome

The goal of this study was to identify recurrent regions of genomic gain or loss in giant‐cell tumor of bone (GCTb). Array comparative genomic hybridization (aCGH) was performed for 20 frozen tumor samples of GCTb. A separate subset of 59 GCTb with outcome data was used for validation. The most frequent region of change identified by aCGH was gain of a 1‐Mbp region at 20q11.1. In the validation arm of 59 cases the minimal common region of copy number gain at 20q11.1, seen in 54% of the samples, was BAC clone RP11‐4O9, which contained the genes TPX2 and BCL2L1. For most cases, amplification was restricted to the mononuclear component and was not present in the multinucleated giant cells. Southern blot for TPX2 and BCL2L1 identified the former as the gene with the highest level of amplification for these two proposed candidate genes of importance. Immunohistochemistry for TPX2 expression correlated with amplification, while BCL2L1 expression was not identified. Kaplan–Meier curves for progression‐free survival showed a statistically significant difference for cases with 20q11.1 amplification (P = 0.0001). Univariate analysis involving Cox proportional hazards models did not show a significant difference for initial treatment type (curettage versus resection) (P = 0.575), age (≤50 vs. >50) (P = 0.543), or sex (P = 0.268), but did correlate with 20q11.1 amplification (P = 0.001). By multivariate analysis, it was found that 20q11.1 amplification (P = 0.001) was the only factor to reach statistical significance. 20q11.1 amplification can be used as a marker of prognostic importance in GCTb. We propose TPX2 as a candidate oncogene in the core‐amplified region at 20q11.1.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

MYC Amplification and Polysomy 8 in Chondrosarcoma: Array Comparative Genomic Hybridization, Fluorescent In Situ Hybridization, and Association With Outcome

PURPOSE To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion. MATERIALS AND METHODS Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation. RESULTS Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance. CONCLUSION MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.

Diagnosis and Management of Soft-tissue Masses

Soft-tissue masses of the extremities are common entities encountered by nearly all providers of musculoskeletal patient care. Proper management of these lesions requires a specific process of evaluation. A detailed history and physical examination must be performed. Appropriate imaging studies must be obtained based on clinical indications. MRI is the imaging modality of choice for diagnosis of soft-tissue masses, with CT and ultrasonography used as secondary options. These modalities aid the clinician in developing an appropriate differential diagnosis and treatment plan. When the initial evaluation is inconclusive, biopsy must be performed. A diagnosis must be established before definitive treatment with surgical excision or, in rare cases, radiation therapy is performed. Clinicians without substantial experience in treating soft-tissue masses should consider referral to a musculoskeletal oncologist for specialized care when a definitive diagnosis of a benign lesion cannot be made. Several studies have shown that multidisciplinary care in specialized referral centers optimizes outcomes and diminishes comorbid complications.A retrospective review of twenty-one patients with Olliers disease showed that the lesion involved the femur and tibia most frequently, and that those bones accounted for the large majority of clinical problems. Angular deformities were common; 80 per cent of the affected femora had clinically significant varus or valgus angulation in the distal part and 42 per cent of the affected tibiae had proximal or distal deformity. The apex of the angulation, when present, was metaphyseal, with the concavity on the side that was more extensively involved by the enchondromas. Osteotomies were done frequently to correct angulation; all healed well. Deformity in the distal part of the femur frequently required repeat osteotomy to achieve a straight bone at skeletal maturity, The extent of shortening, which always was present in the involved limb, closely paralleled the extent of involvement, The discrepancies in limb lengths prior to surgical treatment averaged 9.8 centimeters (range, 4.3 to 35.7 centimeters). Epiphyseal arrest, when appropriately timed, was effective in correcting or limiting the discrepancies, but partial (medial or lateral) epiphyseal arrest to correct angular deformity was ineffective. Diaphyseal lengthening was done on six occasions, once in the femur and five times in the tibia and fibula, with good results. Fourteen pathological fractures occurred in seven of the twenty-one patients, and all healed uneventfully with conservative treatment.

The cytopathology of soft tissue mxyomas: ganglia, juxta-articular myxoid lesions, and intramuscular myxoma.

We studied the practicality of issuing a cytologic diagnosis of myxoma/juxta-articular myxoid lesion/ganglion (MJG) by reviewing all fine-needle aspiration (FNA) biopsy specimens of soft tissue masses in our files with diagnoses of myxoma, myxoid cyst, myxoid lesion, ganglion, or ganglion cyst. The control group was soft tissue aspirates with abundant myxoid stroma. Of 39 cases with a cytologic diagnosis of soft tissue MJG, 15 had subsequent tissue biopsy or complete resection of the mass; 24 had clinicoradiologic follow-up. All cases except 1 (fat necrosis) were diagnosed correctly as benign myxoid lesions. We grouped MJG aspirates into 3 subtypes based on clinicoradiologic features: soft tissue ganglion/ganglion cyst (12 cases), juxta-articular myxoid lesion (16 cases), and intramuscular myxoma (11 cases). MJG aspirates showed few, subtle cytopathologic differences among subtypes. They characteristically had a viscous, gelatinous quality when expressed from the needle onto the glass slide. The typical smear contained a film of paucicellular, often finely granular, myxoid stroma, that contained few cells, usually macrophages or bland spindle cells. Control group aspirates always contained cellular components that allowed distinction from MJGs. The cytopathologic diagnosis of MJG lesions is accurate; FNA biopsy can be used to subtype MJGs into 3 categories when clinicoradiologic features are known.

Nodular Fasciitis of the Hand A Potential Diagnostic Pitfall in Fine-Needle Aspiration Cytopathology

Fine-needle aspiration biopsy (FNAB) is applied very uncommonly to soft tissue masses and even more infrequently to lesions of the hand. Nodular fasciitis, an uncommon pseudosarcomatous lesion of soft tissue, rarely occurs in the hand and, because of this, is not often considered in the differential diagnosis of hand masses. We report 3 cases (2 men and 1 woman; mean age, 44.3 years) of soft tissue masses of the hand, which, after clinical and radiologic evaluation, were strongly suspected by an experienced orthopedic oncologist as harboring a soft tissue sarcoma. Each patient underwent FNAB, which showed markedly hypercellular smears with overlapping, relatively isomorphic spindle cells that were mistaken cytologically as possible sarcoma in 2 cases; 1 case was considered probable nodular fasciitis. All lesions eventually were diagnosed as nodular fasciitis after thorough histologic and immunohistologic evaluation. Nodular fasciitis remains a difficult diagnosis by FNAB, particularly when it occurs in locations such as the hand.

Nodular Fasciitis of the Hand

Fine-needle aspiration biopsy (FNAB) is applied very uncommonly to soft tissue masses and even more infrequently to lesions of the hand. Nodular fasciitis, an uncommon pseudosarcomatous lesion of soft tissue, rarely occurs in the hand and, because of this, is not often considered in the differential diagnosis of hand masses. We report 3 cases (2 men and 1 woman; mean age, 44.3 years) of soft tissue masses of the hand, which, after clinical and radiologic evaluation, were strongly suspected by an experienced orthopedic oncologist as harboring a soft tissue sarcoma. Each patient underwent FNAB, which showed markedly hypercellular smears with overlapping, relatively isomorphic spindle cells that were mistaken cytologically as possible sarcoma in 2 cases; 1 case was considered probable nodular fasciitis. All lesions eventually were diagnosed as nodular fasciitis after thorough histologic and immunohistologic evaluation. Nodular fasciitis remains a difficult diagnosis by FNAB, particularly when it occurs in locations such as the hand.

The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas

Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1−3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2−3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this malignancy.

Internal and external hemipelvectomy or flail hip in patients with sarcomas quality-of-life and functional outcomes

ObjectiveWe evaluated the quality-of-life of patients who have had an internal hemipelvectomy with and without (flail hip) prosthetic reconstruction and external hemipelvectomy. DesignWe reviewed the cases of 15 patients who had undergone either internal or external hemipelvectomy for tumor. Fifteen patients who were previously treated operatively with either a type II periacetabular internal (n = 5) or external (n = 10) hemipelvectomy were evaluated using the Toronto Extremity Salvage Score (TESS), Musculoskeletal Tumor Society (MSTS), and the 36-item Short-Form Health Survey. There were 11 (73%) men and 4 (27%) women in the study, with a mean age at operation of 46.9 ± 18.0 yrs (range, 18–69 yrs). ResultsFollow-up was 30.6 ± 19.6 mos (range, 6–70 mos). Overall mean MSTS score was 45.2 (range, 6.7 to 83.3), and TESS score was 60.4 ± 16.1 (range, 31.8–88.0). The 36-item Short-Form Health Survey physical component score results were lower than the general population. TESS and MSTS were all positively correlated to physical component score. There were no significant influences of postsurgery time on MSTS, TESS, or physical component score. Age had a negative correlation with physical function. ConclusionsQuality-of-life and functional outcome were significantly reduced for patients with internal and external hemipelvectomies on the TESS, MSTS, and the 36-item Short-Form Health Survey physical component scores.

Local recurrence rate of fine‐needle aspiration biopsy in primary high‐grade sarcomas

Fine‐needle aspiration biopsy (FNAB) is an emerging technique for diagnosis of bone and soft tissue lesions. While multiple studies have demonstrated efficacy, cost‐effectiveness, and convenience, none have attempted to determine if the modality leads to an increased rate of local recurrence. Our objective was to determine whether FNAB could be linked to an increased rate of local recurrence.