Richard J. O'Donnell

Recurrence of giant-cell tumors of the long bones after curettage and packing with cement.

The nine-year experience with sixty patients who had had a giant-cell tumor of a long bone was reviewed to determine the rate of recurrence after treatment with curettage and packing with polymethylmethacrylate cement. The demographic characteristics, including the age and sex of the patient and the site of the tumor, were similar to those that have been reported for other large series. An average of four years (range, two to ten years) after the operation, the over-all rate of initial local recurrence was 25 per cent (fifteen of sixty patients). Patients who had had a tumor of the distal aspect of the radius had a higher rate of recurrence (five of ten) than those who had had a tumor of the proximal aspect of the tibia (seven [28 per cent] of twenty-five) or of the distal part of the femur (three [13 per cent] of twenty-three). Higher rates of recurrence were also noted for patients who had had a pathological fracture (three of six), those who had had a Stage-III tumor according to the classification of Campanacci et al. (six of sixteen), and those who had not had adjuvant treatment with either a high-speed burr or phenol (eight of nineteen). Patients who had had an initial recurrence after packing with cement had a low rate of secondary recurrence when the initial recurrence had been treated with a wide resection or a second intralesional procedure (zero of ten and one of five patients, respectively), after an average of three years (range, ten months to eight years). No patient had a multicentric tumor or metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Late recurrence of giant-cell tumor of bone. A report of four cases.

CASE 1 . A thirty-three-year-old man was examined at another institution in 1973 because of pain in the left knee. Radiographs revealed a lytic expansile lesion in the distal metaphysis of the left femur. The diagnosis of giant-cell tumor of bone was established on the basis of biopsy findings. The lesion was curetted and the cavity was filled with corticocancellous bone from the iliac crest. The postoperative course was uneventful. and the patient resumed full activity. The patient remained asymptomatic for nineteen years, until July 1992. when he noted progressively worsening pain with activity in the anterior and lateral aspects of the left knee. A clinical examination revealed no clicks, meniscal signs, or evidence of instability, but the passive range of motion was mildly limited. A firm region in the suprapatellar pouch was thought to represent synovitis. Radiographs demonstrated incorporation of the bone graft, and no definite lytic lesion was identified. Magnetic resonance imaging demonstrated an increased T2 signal in the subchondral region of the distal part of the femur; this finding was consistent with recurrent giant-cell tumor along the distal margin of the incorporated bone graft. A bone scan indicated a single focus of increased uptake in the lateral condyle of the femur. Laboratory evaluation revealed normal findings except for an elevated erythrocyte sedimentation rate of twenty-two millimeters per hour (normal, ten to twenty millimeters per hour). The results of an open biopsy were consistent with recurrent benign giant-cell tumor of bone. The incision was extended and the subchondral region of the femoral condyle was curetted aggressively and packed with polymethylmethacrylate cement. The postoperative course was uncomplicated, and the patient was free of discomfort six months after the operation. At that time, he walked independently and had no ligamentous laxity; the passive range of motion of the knee was 10 to 1 10 degrees. No evidence of progressive lucency, suggestive of another recurrence, was seen radiographically.

Prevention of orthopaedic implant infection in patients undergoing dental procedures

&NA; The Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures evidence‐based clinical practice guideline was codeveloped by the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association. This guideline replaces the previous AAOS Information Statement, “Antibiotic Prophylaxis in Bacteremia in Patients With Joint Replacement,” published in 2009. Based on the best current evidence and a systematic review of published studies, three recommendations have been created to guide clinical practice in the prevention of orthopaedic implant infections in patients undergoing dental procedures. The first recommendation is graded as Limited; this recommendation proposes that the practitioner consider changing the long‐standing practice of routinely prescribing prophylactic antibiotic for patients with orthopaedic implants who undergo dental procedures. The second, graded as Inconclusive, addresses the use of oral topical antimicrobials in the prevention of periprosthetic joint infections. The third recommendation, a Consensus statement, addresses the maintenance of good oral hygiene.

Oncologic Approaches to Pediatric Limb Preservation

Abstract Preservation of limb function in the pediatric oncology patient is uniquely challenging. Treatment must be strictly prioritized in terms of the patients life, the limb, its function, length equalization, and cosmetic appearance. At the same time, social, socioeconomic, and cultural factors must be understood and respected to achieve the most advantageous outcome for both the patient and family. Given these considerations, as well as the relative rarity of many oncologic diagnoses and the myriad of presentation scenarios, drafting generalized treatment recommendations is difficult. Instead, orthopaedic intervention in the care of children and young adults with oncologic conditions must be individualized, with the broad goal being optimization of limb function rather than rigid advocacy of limb salvage.

Giant Cell Tumor of Bone in the Foot and Ankle

Giant cell tumor of bone has been shown to behave more aggressively when located in the wrist and hand. Although nearly 4% of giant cell tumors arise in the foot and ankle, biological features specific to this location have not been identified. In our experience with more than 300 cases of giant cell tumor, 12 arose in the foot and ankle and were followed for more than 2 years. These included nine females and three males ranging in age from 15 to 52 years (mean age, 29.5 years). All patients presented with pain of 5.0 months’ mean duration and 9 of 12 tumors demonstrated aggressive radiographic features, including bone erosion and destruction; five had either invasion of a joint or a soft tissue mass present. Unlike the hand, where metacarpal and phalangeal lesions are common, no tumors arose in the forefoot and nine of the tumors were present in the ankle region. Four patients were treated with resection (no recurrence), two with curettage and cement packing (one recurrence), and six with curettage and autologous bone graft (two recurrences), which resulted in an overall recurrence rate of 25%. None of the recurrent tumors have returned after additional treatment, which consisted of curettage and cement packing in two cases and resection in one case. Five tumors (four primary, one recurrent) were treated with local resection and reconstruction with no major complications and with no amputations performed. Thus, giant cell tumors of the foot and ankle can be treated with local procedures, which result in recurrence rates similar to those found in more common locations.

Utility of Immunohistochemistry for Endothelial Markers in Distinguishing Epithelioid Hemangioendothelioma From Carcinoma Metastatic to Bone

CONTEXT Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm of intermediate malignancy. Epithelioid hemangioendothelioma often presents a difficult diagnostic problem, especially in bone, because the epithelioid morphology and radiographic features raise the possibility of metastatic carcinoma. The current trend of small biopsies obtained with computed tomography-guided techniques exacerbates the problem. The markedly different treatment for EHE and metastatic carcinoma underscores the need for specific markers that can differentiate between these 2 entities. OBJECTIVE To determine the relative utility of endothelial markers in differentiating EHE from metastatic carcinoma, with emphasis on bone biopsies. DESIGN We used immunohistochemistry in formalin-fixed paraffin-embedded tissue to compare the utility of Fli-1, CD34, CD31, podoplanin, and keratin cocktail in 13 EHEs and 13 morphologically similar carcinomas metastatic to bone. Immunohistochemical data were evaluated using Fisher exact test, and specificity and sensitivity were calculated. RESULTS Significant proportions of EHEs were positive for Fli-1 (100%), CD34 (85%), and CD31 (100%) compared with metastatic carcinoma (Fli-1, 15%; CD34, 15%; CD31, 38%) (P < .001, P = .005, and P = .01, respectively). However, these markers were not 100% specific for EHE. Cytokeratin cocktail stained significantly more metastatic carcinomas (100%) than EHEs (38%) (P = .01) but was not 100% specific. No significant difference was observed regarding immunostaining for podoplanin between the tumor types. CONCLUSIONS Fli-1 is most helpful in distinguishing EHE from metastatic carcinoma. However, the absence of complete specificity of any of the endothelial markers for EHE, or of keratin cocktail for carcinoma, suggests that these markers are best used in combination.

β-Catenin Nuclear Expression Correlates With Cyclin D1 Expression in Primary and Metastatic Synovial Sarcoma: A Tissue Microarray Study

CONTEXT The association between aberrant (nuclear) beta-catenin expression and cyclin D1 accumulation has been demonstrated in diverse neoplasms. In synovial sarcoma (SS), aberrant beta-catenin expression has prognostic relevance, but the association with cyclin D1 has not been established. The SYT-SSX fusion protein, unique to SS, may independently increase cyclin D1. OBJECTIVE To determine whether nuclear beta-catenin is associated with cyclin D1 overexpression in SS and whether primary and metastatic SS differ in the expression of these markers. DESIGN We incorporated 82 tumors initially diagnosed as SS into a tissue array. Fluorescence in situ hybridization with custom probes was used to select t(X;18) positive tumors. Clinical data, tumor type and outcome were tabulated. The tumors were tested for the association between nuclear beta-catenin and cyclin D1 immunostaining. Primary and metastatic tumors were compared. RESULTS Fifty-one tumors (41 primary and 10 metastatic) from 43 patients demonstrated t(X;18). Cyclin D1 staining was identified in 21 (59%) primary and 8 (80%) metastatic tumors, respectively, and nuclear beta-catenin in 24 (41%) primary and 7 (70%) metastatic tumors, respectively. No significant difference was noted between primary and metastatic tumors with respect to the above markers. The presence of nuclear beta-catenin showed a significant association with cyclin D1 expression (P < .001). A small number of cyclin D1 cases were negative for nuclear beta-catenin but positive for phosphorylated Akt. CONCLUSIONS Increased cyclin D1 in SS may be driven by abnormally expressed beta-catenin, similar to other neoplasms. The pattern of expression of these markers is established early during tumorigenesis.

Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma

Liposarcoma represents a unique model insofar as some well-differentiated liposarcomas progress to non-lipogenic, so-called ‘dedifferentiated,’ forms. The well-differentiated and dedifferentiated family of liposarcomas demonstrates amplification of the chromosome subregion 12q13–q15 with resultant amplification of the MDM2 and CDK4 genes. However, the specific genetic changes that distinguish between well-differentiated and dedifferentiated liposarcomas are less well understood. To study the genetic changes in dedifferentiated liposarcomas, paired well-differentiated and dedifferentiated components of 29 tumors were analyzed separately by array-based comparative genomic hybridization. A bacterial artificial chromosome array at ∼1-Mb resolution was used. The genetic changes were compared with clinical presentation, grade of the dedifferentiated component and overexpression of MDM2 and CDK4. Most tumors (n=21, 72%) were retroperitoneal, with both components present at initial diagnosis (n=25, 86%). Eight tumors (28%) were classified as low-grade dedifferentiation. In four cases (14%), a well-differentiated liposarcoma preceded the presentation of the dedifferentiated tumor by 1–5 years. 12q13–q15 was amplified in all tumors. Using unsupervised hierarchical clustering of copy-number changes, all but two tumors showed close similarities between well-differentiated and dedifferentiated components, and segregated as pairs. Dedifferentiated components had more total amplifications (P=0.008) and a trend for gain at 19q13.2, but no genetic changes were significant in distinguishing between the two components. High-level amplifications of 1p21–32 (n=7, 24%), 1q21–23 (n=9, 31%), 6q23–24 (n=6, 21%) and 12q24 (n=3, 10%) were common, but none significantly correlated with differentiation. Presentation and grade correlated with the frequency of changes at a number of genetic loci (P<0.001), whereas CDK4 immunostaining showed negative correlation with 12q13.13 amplification. The genotypic similarity, at the limit of the arrays resolution, between components implies that most genetic changes precede phenotypic ‘progression,’ early in tumorigenesis. The relationship between genetic changes and presentation or grade may reflect differences in factors that control genomic instability or the background genotype of the tumor.

Effect of chemotherapy on initial compressive osseointegration of tumor endoprostheses

Chemotherapy has long been suspected of having an adverse effect on bone healing. Massive tumor endoprostheses which achieve osseointegration via compressive force provide a unique model to study the effects of chemotherapy on bone healing. We compared distal femoral bone hypertrophy in patients who received chemotherapy with those who did not. Fifty four patients underwent distal femoral reconstruction with a compression implant. Thirty patients received chemotherapy (Group 1), and 24 did not (Group 2). The group of patients receiving chemotherapy was younger, had lower body mass indices, and had different diagnoses compared to the group of patients not receiving chemotherapy. We used a standardized technique to measure bone growth at the bone-prosthetic interface. The rate of cortical width increase at the bone-prosthetic junction was faster in Group 2 compared to Group 1. Similarly, the increase in cortical width from immediate postop to 3 months and 6 months postop was greater in Group 2 when compared to Group 1. The data suggest chemotherapy administration for musculoskeletal malignancy has a substantial initial adverse effect on bone hypertrophy and a trend towards reduced prosthetic survival. These findings have important implications for the patients with musculoskeletal tumors.Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.