Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma.

Overexpression of the HER-2/neu oncogene appears to have prognostic significance in breast cancer. Recently, some have reported a relationship between increased immunohistochemical expression in osteosarcoma and poor clinical outcome. Despite limited data, a pilot trial of Herceptin, which targets the oncogene product, has been initiated for the therapy of some metastatic osteosarcomas (CCG-P9852). Archival formalin-fixed, paraffin-embedded tissue obtained from 41 patients diagnosed with osteosarcoma was examined immunohistochemically by 2 antibodies against the HER-2/neu oncogene product: CB-11 (monoclonal, 1/100) and Oncor (polyclonal, 1/200). All but one tumor (case of recurrent dedifferentiated parosteal osteosarcoma) represented primary tumor samples; when applicable, only prechemotherapy biopsies were analyzed. The study sample included the full spectrum of histologic subtypes and grades of osteosarcoma (25 conventional high grade; 3 telangiectatic; 1 small cell; 6 parosteal; 1 periosteal; and 5 low-grade intramedullary). A case of metastatic breast cancer with known overexpression of the HER-2/neu oncogene served as the positive control. Complete membranous positivity, considered prognostically significant in breast cancer, was not seen in any of our osteosarcoma cases. At least focal cytoplasmic positivity was documented in 40 (98%) tumors using the CB11 antibody and in 34 (83%) using the Oncor antibody. The intensity of the cytoplasmic staining (0, 1-3+) did not correlate with histologic subtype/grade, response to chemotherapy (<90% versus > or = 90% necrosis), metastasis, or survival. Immunohistochemical overexpression of the HER-2/neu oncogene, defined as complete membranous positivity, is not present in our series of osteosarcomas. Cytoplasmic positivity is observed in most osteosarcomas, irrespective of histologic subtype/grade, and is not associated with response to preoperative chemotherapy or disease progression.

The use of vacuum-assisted closure therapy for the treatment of lower-extremity wounds with exposed bone.

Lower-extremity wounds with exposed tendon, bone, or orthopedic hardware present a difficult treatment challenge. In this series of patients, subatmospheric pressure therapy was applied to such lower-extremity wounds. Seventy-five patients with lower-extremity wounds, most of which were the result of trauma, were selected for this study. Dressings made of sterile open-cell foam with embedded fenestrated tubing were contoured to the wound size and placed into the wound. The site was covered with an adhesive plastic sheet. The sheet was placed beneath any external fixation devices, or the fixation device was enclosed within the sheet. The tubing was connected to the vacuum-assisted closure pump. Continuous subatmospheric suction pressure (125 mmHg) was applied to the wound site. The wounds were inspected and the dressings were changed every 48 hours.Vacuum-assisted closure therapy greatly reduced the amount of tissue edema, diminishing the circumference of the extremity and thus decreasing the surface area of the wound. Profuse granulation tissue formed rapidly, covering bone and hardware. The wounds were closed primarily and covered with split-thickness skin grafts, or a regional flap was rotated into the granulating bed to fill the defect. Successful coverage was obtained without complication in 71 of 75 patients. Wounds have been stable from 6 months up to 6 years.

Intraosseous radial nerve entrapment complicating total elbow revision.

A 43-year-old man underwent revision of a loose total elbow arthroplasty in 1995. The arthroplasty had been implanted 20 years previously for post-traumatic osteoarthritis after a gunshot wound complicated by permanent ulnar nerve palsy. The patient suffered a minimally displaced periprosthetic fracture 4 years after implantation that was treated closed. The patient subsequently developed severe loosening with bony dilation. During revision surgery, while grasping and removing the periprosthetic membrane from within the humeral medullary canal with a Kerrison rongeur, dorsiflexion of the wrist and hand occurred. Close inspection of the membrane revealed that the radial nerve was encased inside the bone. Although not divided, the traction and contusion of the nerve caused a radial nerve palsy that partially resolved by 4 years of follow-up.

The role of fine needle aspiration biopsy in the diagnosis and management of osteosarcoma.

We retrospectively reviewed our experience with fine needle aspiration biopsy (FNAB) in the diagnosis and management of skeletal osteosarcoma. The bi-institutional study sample involved 30 consecutive aspirates from 29 patients (28 primary tumors, 1 pulmonary metastasis, 1 local recurrence). There were 17 children and 12 adults. Two aspirates were unsatisfactory for diagnosis. Of the adequate primary osteosarcoma cases analyzed by FNAB, 24 of 26 were diagnosed as osteosarcoma. All pediatric cases were correctly interpreted as osteosarcoma and treated appropriately. There were 2 incomplete diagnoses. A secondary osteosarcoma arising within an otherwise clinically, radiologically, and histologically typical giant cell tumor (malignant giant cell tumor) was not diagnosed preoperatively on FNAB due to nonrepresentative sampling. Chronologically, the first patient with osteosarcoma analyzed by FNAB was diagnosed simply as "spindle cell neoplasm." No complications resulted from the procedure. With adequate clinical and radiologic correlation, FNAB represents a technically, easily performed, cost-effective, and accurate procedure for establishing the diagnosis of skeletal osteosarcoma. Immediate interpretation of aspirated material allows for therapy planning and oncologic consultation at the initial clinic visit.

Fine-needle aspiration biopsy of sarcomas and related tumors.

BACKGROUND: Largely due to a lack of experience, familiarity, and/or confidence, few centers rely on simple fine-needle aspiration biopsy (FNAB) for the diagnosis of sarcomas and related tumors. METHODS: The authors have reviewed their own experience in more than 200 cases of FNAB of bone and soft-tissue tumors, as well as cases reported in the literature. RESULTS: FNAB has proven to be accurate and useful in 8 consecutive years of clinical experience. No serious complications have occurred. CONCLUSIONS: FNAB is recommended as an integral part of the initial evaluation of amenable orthopaedic tumors, including sarcomas, especially in cases with classic clinical and radiographic findings.

Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients.

We reviewed the clinicopathologic features of 145 consecutive fine-needle aspiration biopsy (FNAB) specimens from 140 patients without a previous diagnosis of sarcoma. Among 138 adequate specimens, 42 bone sarcomas and 80 soft tissue sarcomas were recognized as sarcomas; histologic subtyping was easier in bone than in soft tissue sarcomas and in pediatric than in adult cases. There was no correlation in accuracy of subtyping in low- vs high-grade sarcomas. FNAB was most accurate for subtyping of skeletal osteosarcoma, pediatric small round cell bone/soft tissue sarcomas, synovial sarcoma, skeletal chondrosarcoma, and adult myxoid soft tissue sarcomas. Although almost always recognized as sarcoma, subtyping of adult pleomorphic soft tissue sarcomas generally was not possible but did not influence therapy; all were considered high-grade sarcomas for treatment purposes. There were 4 misinterpretations of subtype in soft tissue sarcomas; none resulted in a change in therapy. Cytogenetic analysis on aspirated material confirmed t(11;22) in 2 Ewing and t(X;18) in 3 synovial sarcomas. No procedure-related complications occurred. Among bone and soft tissue sarcomas, FNAB was sufficient for initiation of definitive therapy in 87% and 83% of patients, respectively. Most FNAB specimens from bone and soft tissue sarcomas are recognized easily as sarcoma, but subtyping seems more accurate in bone sarcomas. Although histologic subtyping of adult soft tissue sarcomas is often impossible, no influence on initial therapy is usually observed. In contrast, subtyping of pediatric sarcomas by FNAB seems highly accurate and is necessary for appropriate therapy.

Medical management of metastatic skeletal disease.

The medical management of metastatic disease generally includes chemotherapy, hormonal therapy, and metabolic pharmacologic manipulations with medications, such as bisphosphonates as well as nonoperative physical measures, such as orthoses and ambulatory or mobility aids. This comprehensive complex care is best coordinated with the medical oncologist. If well planned and coordinated, such care can improve the life of the cancer patient greatly.

Metastatic disease of the femur. Surgical management.

Treatment of actual or impending pathologic fractures of the femur provides the senior author with some of the most rewarding surgical interventions of his practice. The patients' survival outlook is not changed, but their quality of life is enhanced significantly. Most health care providers usually provide the metastatic cancer patient only temporary symptomatic relief, at best, and often at the expense of continued pain, suffering, or sickness, such as is seen with chemotherapy-associated morbidity. Patients with metastatic bone disease are usually incredibly grateful for the restoration of function and diminution of their pain that results from the proper operation on metastatic bone disease. These patients typically are among the most appreciative patients and often express their gratitude when seen in follow-up in the clinic or office. Despite their metastatic disease state, their usual enthusiasm is uplifting to the surgeon and to the staff. To help a patient be pain-free and functional in the waning days of his or her life affords the patient, the physician, and the physician's staff with an emotionally rewarding experience and one that is well worth the time and effort required to care for these patients. By following the techniques outlined in this article, most patients with metastatic disease of the femur can be appropriately managed with excellent results.

Femoral recon nails for metastatic disease: indications, technique, and results.

The senior author has used 41 femoral recon nails of one design in 41 consecutive patients with 30 impending and 11 pathologic femur fractures. All nails were inserted with minimally invasive surgical technique. The hospital stay was shorter (average, 5.6 days) and discharge to home was more likely (77%) after stabilization of impending pathologic fractures compared with fixation of completed fractures (length of hospital stay averaged 7.8 days, with a 36% discharge-to-home rate), as patients with completed fractures required a higher level of postoperative care. Fixation prior to fracture occurrence results in predictably better early results than that of fixation after fracture occurrence, confirming the benefit of prophylactic fixation of impending pathologic fractures. To date, there have been no fixation failures and only one significant complication: a nonfatal pulmonary embolus. This technique provides a safe and effective method of stabilizing properly selected femoral lesions resulting from metastatic disease, especially impending pathologic fractures.

The value of fine-needle aspiration biopsy in the differential diagnosis of adult myxoid sarcoma.

BACKGROUND: The usefulness of fine-needle aspiration biopsy (FNAB) for the histologic subtyping of specific sarcomas still is somewhat controversial but is becoming increasingly popular in the U.S. METHODS: To determine the accuracy and usefulness of FNAB in the differential diagnosis of myxoid sarcoma, the authors retrospectively reviewed 18 FNAB specimens (16 primary tumors, 1 local recurrence, and 1 metastasis) in 18 patients. The study sample included myxoid/round cell liposarcoma in six patients, myxofibrosarcoma in six patients, myxoid chondrosarcoma in five patients, and myxoid leiomyosarcoma in one patient. RESULTS: All but one tumor were recognized correctly as malignant. With regard to primary tumors, a specific cytologic diagnosis was rendered in 13 of 16 patients (81%). Problematic areas included the diagnosis of high grade myxofibrosarcoma with minimal amounts of myxoid stroma, myxoid liposarcoma with a predominant round cell component, and the single case of myxoid leiomyosarcoma. CONCLUSIONS: FNAB represents a valuable diagnostic tool for the differential diagnosis of myxoid sarcoma, especially myxofibrosarcoma, low grade myxoid liposarcoma, and myxoid chondrosarcoma. Due to its prognostic and therapeutic significance, the presence of a predominant round cell component in myxoid liposarcoma should be documented adequately. Other sarcomas (e.g., leiomyosarcoma) rarely may exhibit a prominent myxoid stroma and therefore should be considered in the differential diagnosis of adult myxoid sarcoma.

Fibrocartilaginous mesenchymoma of bone: case report and review of the literature.

Fibrocartilaginous mesenchymoma of bone is a rare primary neoplasm. Our literature search produced only 12 previously reported cases. Radiographic and computed tomography (CT) findings have been described, but the magnetic resonance imaging (MRI) appearance has not been reported previously. We report a patient with fibrocartilaginous mesenchymoma of the ilium and describe the imaging findings on conventional radiography, bone scan, CT, and MRI.

Loose fragments and other debris: miscellaneous synovial and marrow disorders.

Conventional MR imaging evaluation of the knee focuses mainly on the effects of acute trauma and degenerative conditions. Numerous other conditions that affect the knee may mimic clinical characteristics of common traumatic and degenerative disorders. Synovial and marrow abnormalities are frequently encountered and often unsuspected on routine MR imaging studies of the knee. This article presents the MR imaging appearance of the normal synovium, bone marrow, and commonly encountered abnormalities of these structures.

Expandable endoprosthesis reconstruction in skeletally immature patients with tumors.

Between September 1984 and January 1996, 32 expandable endoprostheses were used for limb reconstruction after resection of malignant bone tumors in patients who were skeletally immature. The 20 boys and 12 girls ranged in age from 3 to 15 years (mean, 9.7 years). One patient had a Stage IIA tumor, 22 patients had Stage IIB tumors, and seven patients had Stage III tumors according to the classification of the Musculoskeletal Tumor Society. There also were two patients with parosteal osteosarcomas. The histologic diagnosis was osteosarcoma in 23 patients and Ewing's sarcoma in nine. All patients except the patients with parosteal osteosarcoma received standard neoadjuvant therapy. Twenty-two Lewis Expandable Adjustable Prostheses, four modular Wright Medical prostheses, four modular Howmedica prostheses, and two Techmedica expandable prostheses were used. Thirteen patients died, two have no evidence of disease, and 17 are continuously disease free. Sixteen of 32 patients (50%) have not had an expansion procedure because of early death in 10 and early amputation in three. Three patients are waiting to undergo an expansion procedure. Sixteen of the 32 patients (50%) have undergone 32 expansion procedures, to a maximum of 9 cm, without any infection. To maintain range of motion before the expansion procedure, a complete resection of the pseudocapsule was done routinely. Fourteen of the 32 patients did not have complications. Eighteen of the 32 patients had 27 complications. All Lewis Expandable Adjustable Prosthesis endoprostheses and the two nonmodular Techmedica prostheses were associated with a large amount of titanium debris. The children's functional results were similar to the results reported for adults with an average Musculoskeletal Tumor Society rating of good to excellent at the knee, fair to good at the hip, and fair about the shoulder. Rehabilitation of the knee in very young patients (5-8 years) remains problematic and careful selection of patient and family is necessary. The Lewis Expandable Adjustable Prosthesis probably should be reserved for very young patients (5-8 years) and modular systems should be used for large preadolescent and adolescent children.

Fine needle aspiration biopsy of primary bone tumors.

A review of 66 consecutive fine needle aspiration biopsies of primary bone tumors revealed that 48 (73%) were diagnostic. Twelve (18%) yielded inadequate specimens unsatisfactory for diagnosis, and five (8%) yielded specimens adequate for partial diagnosis. The only error, presumably attributable to sampling error, was an unappreciated dedifferentiated osteosarcoma arising in an otherwise typical giant cell tumor. Fine needle aspiration biopsy obviated the need for open biopsy in 24 patients and simplified surgery in an additional 24 patients by establishing the diagnosis before surgical intervention. A solitary soft tissue recurrence of a giant cell tumor has been the only local recurrence. A review of 26 consecutive patients with osteosarcoma revealed that seven tumors were diagnosed by primary open biopsy. Nineteen patients had fine needle aspiration biopsy, of which 15 were diagnostic and four required supplemental open biopsy. The elapsed time between the initial office visit and the diagnostic confirmation averaged 5 days for patients requiring open biopsy compared with 0 days for patients whose fine needle aspiration biopsy was diagnostic. The total estimated charge for fine needle aspiration biopsy of a distal femoral osteosarcoma was $1060.00 compared with $4312.25 for open biopsy. There have been no local recurrences in patients in either group. Fine needle aspiration biopsy provides an accurate, safe, efficient, well tolerated, and cost-effective method for diagnosing classic primary bone tumors, including osteosarcoma.

Fine-needle aspiration biopsy of soft tissue sarcomas. A cytomorphologic analysis with emphasis on histologic subtyping, grading, and therapeutic significance.

Because therapy for sarcoma often incorporates histologic subtype, grade, stage, and anatomic location, establishing a specific histologic subtype often is essential. To evaluate the effectiveness of fine-needle aspiration biopsy (FNAB) in histologic subtyping of soft tissue sarcomas, we retrospectively reviewed 73 consecutive aspirates from 67 patients, none of whom had a previously established sarcoma diagnosis. Sarcoma cases were subgrouped according to predominant cytomorphologic features: pleomorphic cell, 19; small round cell, 18; spindle cell, 18; myxoid, 10; epithelioid/polygonal cell, 7; 1 case of well-differentiated liposarcoma was analyzed separately. Ancillary studies were used for 25 cases. Among adequate specimens, 61 tumors were recognized as sarcoma. A specific and accurate histologic subtype was determined in 34 cases. Ancillary studies were most useful for histologic subtyping of small round cell and spindle cell sarcomas. Myxoid sarcomas were subtyped easily based solely on histomorphologic features. Pleomorphic cell and epithelioid/polygonal cell sarcomas were recognized easily as malignant but difficult to subtype by FNAB. With the exception of small round cell sarcomas, histologic subtyping of a sarcoma usually did not directly influence therapy. With meticulous attention to clinicopathologic features and ancillary techniques, many sarcomas, especially small round cell, spindle cell, and myxoid types, may be subtyped successfully by FNAB, within limitations.

Endoprosthetic reconstruction for malignant upper extremity tumors.

Between December 1980 and December 1992, 59 patients underwent 60 reconstructions with endoprostheses after resection of malignant tumors in the upper extremity. There were 32 male patients and 27 female patients, with a mean age of 33 years (range, 3-83 years). The type of reconstruction was based on the location of the primary tumor site. The histologic diagnoses included osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma, soft tissue sarcoma, and fibrosarcoma of bone. Most of the patients had Stage IIB disease (N = 38), as established by the Musculoskeletal Tumor Society classification. An additional six patients had metastatic tumors to the upper extremity. Twenty-seven of 59 patients died of disease progression. Two patients died of other causes (chronic leukemia, human immunodeficiency virus infection). The 30 survivors had a mean followup of 90 months (range, 60-170 months). The Musculoskeletal Tumor Society functional analysis for the patients with a minimum 2-year followup (N = 41) averaged 74%. Sixteen of the 59 (27%) patients had local complications. Problems related to mechanical failure and infection were managed successfully with second operation. Amputation was rare, occurring in three of 60 (5%) patients and was related only to local recurrence. Endoprosthetic reconstructions of the upper extremity after tumor resections have proven to be successful.

Orthopaedic oncology for the nononcologist orthopaedist: introduction and common errors to avoid.

A number of the more frequently encountered diagnostic and management errors and pitfalls have been discussed. However, if a physician will recognize his or her own limits and will always consider the diagnostic possibility of a neoplastic process, then appropriate steps can usually be taken, improving the patient's health care. The following chapters will outline the appropriate steps in the evaluation and work-up of patients with suspected tumors, as well as the currently recommended approach for biopsy, treatment, and follow-up.

Appropriate follow-up of orthopaedic oncology patients.

In summary, there is no gold standard of the appropriate follow-up of orthopaedic patients. Patients with musculoskeletal neoplasms should be watched closely for local recurrence. Those patients whose tumors have metastatic potential should be followed up closely for metastatic disease. The timing of the suggested follow-up intervals varies, depending on the aggressiveness and growth rate of the tumor. There is no objective, data-based study to define the optimal follow-up intervals for the various entities. In general, the earlier recurrent or progressive disease can be detected, the better the chance of disease eradication. However, there is still some question as to whether the earlier detection of metastatic disease will change the eventual outcome in these patients.

Myxofibrosarcoma of soft tissues: cytomorphologic analysis of a series.

Within the English literature, myxofibrosarcoma is a recently described entity. Although the histopathologic features have been reported, the cytomorphologic spectrum of myxofibrosarcoma has been far less documented. The cytologic findings of six fine-needle aspiration biopsy specimens (five primaries, one local recurrence) from six patients are described. The patients' ages ranged from 26-77 yr; there were four women and two men. The aspiration biopsy specimens ranged from slightly to markedly cellular. Although a myxoid granular to filamentous background was observed at least focally in all cases, the volume of the myxoid material was inversely proportional to the cellularity and grade of the tumor. Individual tumor cells were round to spindled, often displaying a wide range of cell shapes and sizes. Nuclei were generally large, pleomorphic, and hyperchromatic, frequently containing prominent nucleoli. Cytoplasm ranged from scant to dense and tapering. Multinucleated tumor giant cells were occasionally observed. In general, low- and intermediate-grade myxofibrosarcomas were more easily recognized in cytologic preparations. In contrast, high-grade myxofibrosarcoma was more difficult to specifically subtype and not easily distinguished from other adult pleomorphic sarcomas.