Synovial sarcomas usually metastasize after >5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors.

BACKGROUND: Synovial sarcoma (SS) is a malignant soft tissue sarcoma with a poor prognosis because of late local recurrence and distant metastases. To our knowledge, no studies have minimum follow-up of 10 years that evaluate long-term outcomes for survivors. PATIENTS AND METHODS: Data on 62 patients who had been treated for SS from 1968 to 1999 were studied retrospectively in a multicenter study. Mean follow-up of living patients was 17.2 years and of dead patients 7.7 years. RESULTS: Mean age at diagnosis was 35.4 years (range 6-82 years). Overall survival was 38.7%. The 5-year survival was 74.2%; 10-year survival was 61.2%; and 15-year survival was 46.5%. Fifteen patients (24%) died of disease after 10 years of follow-up. Local recurrence occurred after a mean of 3.6 years (range 0.5-14.9 years) and metastases at a mean of 5.7 years (range 0.5-16.3 years). Only four patients were treated technically correctly with a planned biopsy followed by a wide resection or amputation. Factors associated with significantly worse prognosis included larger tumor size, metastases at the time of diagnosis, high-grade histology, trunk-related disease, and lack of wide resection as primary surgical treatment. CONCLUSIONS: In SS, metastases develop late with high mortality. Patients with SS should be followed for >10 years.

[Giant cell tumor of bone with rapid malignant course]. / Riesenzelltumor des Knochens mit rapid malignem Verlauf.

The case of a 28-year-old male patient with a locally aggressive lesion of the distal tibia is presented. Following the diagnosis of giant cell tumor of bone (GCT) on biopsy and curettage, a rapid malignant course was observed with recurrence 2.5 months later. Multiple metastases appeared 6 months after initial presentation. Following initial chemotherapy according to the COSS protocol and later with carboplatin and VP-16, therapy was changed to Adriamycin and later gemcitabine due to progressive disease. Good palliation was achieved, and the patient felt well with less shortness of breath on exertion and was ambulatory with walking aids. The malignant nature of the tumor was not detected in the initial pathologic examinations. Review of the pathologic material provided histologic clues permitting the diagnosis of a primary malignant GCT with a fibrohistiocytic/fibrosarcomatous component. Malignancy in a giant cell tumor is a much debated diagnostic dilemma when a frank sarcomatous component is lacking. Cytologic atypias and flame-like tufts of infiltration of soft tissue are important clues. Surgical treatment should be commensurate. Monotherapy with Adriamycin or gemcitabine can be considered in order to inhibit the disease progression.

Osseous lesions of the distal ulna: atypical location--unusual diagnosis. Report of three cases with similar imaging and different pathologic diagnoses.

Three cases with destructive bone lesions of the distal end of the ulna caused by different pathologic entities (Ewing's sarcoma, osteosarcoma, rheumatoid pseudotumoral synovitis) are presented, all with similar clinical and comparable x-ray and magnetic resonance imaging features. Although the distal end of the ulna may be resected without significant functional impairment, careful evaluation of treatment strategies compatible with oncologic standards is warranted.

[Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative osteosarcoma study group COSS of 925 patients]. / Neoadjuvante Therapie des lokalisierten Osteosarkoms der Extremitäten. Erfahrungen der Cooperativen Osteosarkomstudiengruppe COSS an 925 Patienten.

BACKGROUND: Owing to twenty years of multicentric interdisciplinary cooperation, the COSS group has been able to collect data on a large group of osteosarcoma patients treated by neoadjuvant therapy. This paper reviews results achieved in patients with localized extremity tumors. INCLUSION CRITERIA: Registration into a completed neoadjuvant COSS-Study. Histologically confirmed, primary, localized, high-grade, central osteosarcoma of an extremity; age < 40 years; no pretreatment; interval diagnosis to chemotherapy < or = 3 weeks; no severe comorbidity. Chemotherapy: HD-methotrexate +/- doxorubicin +/- cisplatin +/- ifosfamide +/- BCD. Scheduled local therapy: Surgery. RESULTS: 925 evaluable patients from 101 institutions. Median age 15 years, m:f 1.4:1. Primary site: femur 510, tibia 251, humerus 100, fibula 51, other 13. Tumor-size < 1/3 of the involved bone 616, > or = 1/3 304. Definitive surgery in 903/925 cases, 443 limb salvage procedures. Good response (> 90% necrosis) in 469/806 (58.2%) evaluated tumors. Median follow-up for surviving patients: 5.42 years. Actuarial survival after 5 and 10 years: 72.5% (95%-CI 69.3-75.7) and 66.3% (62.5-70.0), relapse-free 62.1% (58.7-65.4) and 59.4% (55.8-63.0). 683/925 alive (601 first remission), 242 deceased (212 tumor progression, 30 other causes). 66.2% (97.3%) of all relapses within 2 (5) years. Prognosis correlates with tumor-size (< vs. > or = 1/3: 69.9% vs. 58.3% at 10 years) and -site (tibia: 74.2%, humerus: 54.5%) and -response (good vs. poor: 78.2% vs. 52.5%) (all p < 0.01). Actuarial 10-year survival by response grading I-VI according to Salzer-Kuntschik 80.9%, 82.8%, 71.1%, 60.7%, 47.7%, 27.3%. COSS-studies with preoperative 4-drug therapy more efficacious than less aggressive protocols. No impact of doxorubicin scheduling (sequential: rapid vs. 48 h-continuous infusion) or cisplatin scheduling (randomized: 5 h vs. 72 h-infusion) on prognosis detected. CONCLUSIONS: Intensive multiagent chemotherapy and delayed surgery for localized extremity osteosarcoma led to excellent oncologic results in the COSS-studies. Tumor-size, -site, and -response as well as the intensity of upfront chemotherapy correlated with outcome. Giving doxorubicin and cisplatin by continuous infusions did not result in discernible prognostic disadvantages.

Chondromyxoid fibroma of two thoracic vertebrae.

We report on a case of chondromyxoid fibroma involving two adjacent thoracic vertebrae with features of aggressive behaviour on radiographs, CT and MRI. Histology revealed typical chondromyxoid fibroma with unusually coarse calcifications. Chondromyxoid fibroma of the spine is rare, and only 30 of these tumours have been reported so far. Involvement of two contiguous vertebral bodies by chondromyxoid fibroma, as reported here, appears exceptional.

Analysis of two bone-prosthesis interfaces and membranes from non-cemented trapeziometacarpal prostheses.

The non-cemented Ledoux trapeziometacarpal prosthesis has a high failure rate. In order to better understand the mechanism responsible for pain and loosening, we thoroughly analysed the membranes surrounding the prosthesis and the bone-prosthesis interface in two trapezia, each containing a Ledoux cup, which were resected after unsuccessful implantation. Serial sections, perpendicular to the longitudinal axis of the implanted cup, allowed histological examination of the interface and were used to quantify bone apposition. The tissues surrounding the prosthesis showed a foreign-body reaction to particles identified as titanium. The interface showed bony integration of the cup, mainly on the radial side and on the proximal part of the cup, with an appositional index of 28%. Our findings suggest that bony apposition might not be sufficient to ensure successful anchoring of the Ledoux cup in the trapezium in the presence of an intense foreign body reaction to titanium. Moreover, the presence of metal might be secondary to micromotion of the wings of the metallic part of the cup, induced by axial movement of the underlying polyethylene during pinch grip. The combination of polyethylene as an expander and titanium may need to be reviewed.

[Muscle metastasis as initial manifestation of adenocarcinoma of the stomach]. / Muskel-Metastase als Erstmanifestation eines Adenokarzinoms des Magens.

BACKGROUND: The presentation of gastric carcinoma with a metastasis in skeletal muscle is a distinct rarity. CASE REPORT: In a 72-year-old male patient a soft tissue mass behind the knee was biopsied rather late. Histology showed a metastasis of adenocarcinoma. The patient mentioned a slight feeling of strangulation, which led to endoscopy and the diagnosis of gastric carcinoma. Palliative chemotherapy was initially successful but the patient died after 21 months. DISCUSSION: Based on this case history, three points are discussed: how to biopsy a peripheral soft tissue mass, how to proceed when a metastasis of an unknown primary tumor is diagnosed, and the epidemiology of metastases to skeletal muscle.

[Osteosarcoma and Ewing's sarcoma. Improved recovery chances in the past 25 years according to the experience of Balgrist Hospital]. / Osteosarkom und Ewing-Sarkom. Die verbesserten Heilungschancen in den vergangenen 25 Jahren in der Erfahrung der Klinik Balgrist.

At the Balgrist hospital 38 patients with osteosarcoma and 18 patients with Ewing sarcoma were treated from 1970 through 1992; a follow-up of at least three years is available for all patients. Disease-free survival in this period of time has increased from 20% (Ewing sarcoma) and 30% (osteosarcoma) to over 75%. While systemic tumor control was improved by systematic chemotherapy, local tumor control was improved by appropriate biopsy techniques, and amputations have been replaced by local resections, in most cases with reconstruction (arthrodesis, rotation plasty, endoprosthesis, allografts), which require further improvements. With respect to cure of the neoplastic disease, the currently available methods have been used to their maximum potential, and a steady state has been reached regarding survival. Further improvement of survival will therefore depend on the introduction of completely new modalities.

Hyperostotic and destructive osteoarthritis in a patient with vitamin A intoxication syndrome: a case report.

The authors present a case report of a 59-year-old female suffering from hyperlipidemia who developed chronic vitamin A intoxication syndrome after ingestion of 30,000 IU retinol/daily over a period of six years. The patient's main complaints included severe headaches, morning nausea, myalgias and disability around the hip, knee, and ankle joints. Radiologically, hyperostosis of the acetabular circumference and the spine was demonstrated. Because of rapidly increasing pain, total hip replacement was performed. Histology of cross sections from the femoral head revealed destructive osteoarthritis. Since no other causative reason was found, retinol may not only be responsible for hyperostotic bone and soft tissue formations but may perhaps also account for rapid progressing of degenerative joint disease. Despite the cessation of vitamin A intake the clinical symptoms persisted due to hyperlipidemia. The enlarged number of chylomicrons and the higher fraction of very low density lipoproteins may represent a second retinyl ester pool in case of overloaded fat storing Ito-cells in the liver. Therefore, rheumatological treatment reducing risk factors such as hyperlipidemia is mandatory.

[Penis carcinoma in a young chimney sweep. Case report 200 years following the description of the first occupational disease]. / Peniskarzinom bei jungem Schornsteinfeger. Fallbericht 200 Jahre nach Beshreibung der ersten Berufskrankheit.

We report on a 32-year-old patient who, following exposure to soot over a total of 78 weeks as a professional chimney sweep, developed squamous cell carcinoma of the penis. Since the epoch-making description of occupational cancer of the scrotum by Percivall Pott in 1775, soot-related cancer of the scrotum and penis has become anecdotal. As our patient presented with inguinal lymph node metastases, a wide circumcision was performed, followed by preoperative chemotherapy and bilaterial lymphadenectomy. The patient has been free of disease for over 9 years with no functional loss.

The use of CD31 and collagen IV as vascular markers. A study of 56 vascular lesions.

A monoclonal antibody against the endothelial cell adhesion molecule CD31 (endo-CAM, PECAM-1) was tested on wax embedded tissue of 56 cases of vascular lesions including benign and malignant vascular neoplasms. Additional preparations were stained with antibodies to type IV collagen and to von Willebrand factor/Factor VIII-RAG (vWf). Our results prove reliability of CD31 and its superiority to vWf in the labelling of endothelium and its subsets in such lesions, with the exception of lymphangiomas. As markers for basal lamina collagen and endothelium respectively, type IV collagen and CD31 together provide a powerful tool for 1) the diagnosis of endothelial neoplasms and 2) the definition of endothelial, mural and pericytic or perivascular tissue compartments in vascular lesions of complex architecture. Hence, we use CD31 and type IV collagen in cases of presumed vascular neoplasms, adding other markers to the panel in accordance with the differential diagnosis, as well as in the recognition of compromised endothelia, such as in vascular invasion by various malignant neoplasms.

[Fibrous dysplasia and osteofibrous dysplasia]. / Fibröse Dysplasie und osteofibröse Dysplasie.

Fibrous and osteofibrous dysplasia are benign lesions of the bone involving single bones as monostotic or multiple bones as polyostotic forms. When the patient is in the growth phase, the lesions, which are usually asymptomatic initially, may lead to deformities with typical bowing of the proximal femur ("shepherd's crook") and fractures. It is important to recognize osteofibrous dysplasia of the tibia and fibula, where any surgical measures, even a small biopsy, may activate the process and cause the lesion to grow, although it may spontaneously rest around puberty. Polyostotic fibrous dysplasia may rarely be associated with areas of cutaneous pigmentation and endocrine disturbances, especially precocious puberty (McCune-Albright syndrome).

Reduced vitamin A tolerance in a hyperlipidaemia patient with rapid destructive and hyperostotic osteoarthritis of the hip.

A 59-year-old patient suffering from hyperlipidaemia developed a chronic vitamin A intoxication syndrome after ingestion of 30000 IE retinol/daily over a period of six years. Functional disability of the right hip was caused by radiologically documented hyperostosis of the acetabular circumference. Finally, a prosthesis had to be implanted because of rapid destructive osteoarthritis of the right hip. Implications of vitamin A for rheumatological management are discussed.

[Proliferative myositis--a little-known pseudomalignant lesion]. / Proliferative Myositis--eine wenig bekannte pseudomaligne Läsion.

The leading symptom of proliferative myositis is a rapidly growing hard tumor in the muscle. The disease is rare and therefore widely unknown. We observed a case of proliferative myositis in a 54-year-old female. We initially interpreted the hard tumor in the left musculus sternocleidomastoideus and its rapid growth as a malignant disease. The histological findings finally led to the correct diagnosis. In the light of the literature of 78 reported cases, a presumptive diagnosis can already be suspected from the clinical examination. The addition of CT scan and fine needle aspiration is highly diagnostic.

[Technique and tactics of biopsy including puncture]. / Technik und Taktik der Biopsie incl. Punktion.

The biopsy is the key for the exact diagnosis of bone and soft tissue sarcomas. However the biopsy implicates risks that eventually may significantly interfere with the prognosis. The steps of the biopsy can be differentiated in tactical and technical aspects. Tactical aspects include laboratory examinations (e.g. blood count, immunological, chemical tests) in order to establish the prebiopsy differential diagnosis, basic imaging procedures (bone scan, magnetic resonance imaging) and to discuss with the pathologist questions as which region of the tumor might be most informative, how should the material be preserved and whether a frozen section might be useful and allow for initiation of therapy as early as possible. Furthermore the site of the biopsy has to be carefully chosen, the compartments that need being passed through or opened up during biopsy must be considered. The technical aspects refer to the approach and tissue handling during the biopsy itself. Fine needle aspiration allows only for a cytologic, core biopsies for a histologic examination (however only of a small sample), while the open biopsy provides more material for more analyses. Any biopsy (open biopsy as well as percutaneous puncture) contaminates the path with tumor cells and increases the risk of systemic seeding. In order to keep these risks as small as possible the most careful technique and tissue handling is mandatory. The biopsy path has to be completely ('en bloc') resected later for local tumor control.

[Fatigue fracture as a tumor-simulating lesion. Differential diagnostic delimitation using proton spin tomography]. / Ermüdungsfraktur als tumorvortäuschende Läsion. Differentialdiagnostische Einengung durch die Kernspintomographie.

Fatigue (stress) fractures are due to increased repetitive stresses. The onset of clinical symptoms and the pain characteristic usually are vague; furthermore the radiographic picture shows lesions of different age and therefore may mimic a pattern typical of bone tumors. While for malignant bone tumors early diagnosis, biopsy and initiation of the appropriate treatment is of importance, the biopsy of a fatigue fracture is not only unnecessary, but also may interfere with the healing process. The value of magnetic resonance imaging in the differential diagnosis between tumors and fatigue fractures has therefore been analysed. Five consecutive cases of fatigue fractures have been evaluated from the onset of symptoms for a mean of 19 month (range 3-45 month) of follow-up. The signal pattern with low intensity in the area of the lesion in T1- and T2-weighted images seen in 2 cases has lead to observe the process under immobilization of the affected limb, while because of an increase of the signal intensity from T1- to T2-weighted images as seen in almost all malignant bone tumors biopsy has been performed in 2 cases. In 1 cases no biopsy but close-meshed clinical examinations were performed although there was an increase of the signal. From these observations we conclude that the MRI in fatigue fractures may either show a 'chronic' type of reaction with low signal intensity allowing for the caution observation while in cases with the rather 'acute' reaction with increased signal biopsy usually cannot be avoided in order not to miss a malignant tumor.

Epithelioid sarcoma mimicking angiosarcoma: the value of immunohistochemistry in the differential diagnosis.

Epithelioid sarcoma (ES) is a rare malignant tumour of young adults, usually presenting as a skin ulcer or subcutaneous nodule in the distal portion of the upper limb. Multiple recurrences and late metastases are typical, leading to fatality in a third to one-half of all cases. The slow evolution of the tumour is one reason for its delayed recognition. The other is its frequent histological misinterpretation, in particular, as a peculiar granulomatous reaction. In our case, the primary tumour presented a variant morphological pattern so closely mimicking a cavernous angiosarcoma as to mislead several reputable opinions. Later recurrences and metastases were typical of ES, while a focal angiomatoid pattern was maintained. The morphology and immunoreactivity to a wide spectrum of tumour markers is compared with that of six file cases of classical ES. Retrospectively, all neoplastic lesions in our patient were ES. In young adults, lesions of the upper extremity, even when angiomatoid or haemorrhagic, should raise a suspicion of ES. Once epithelioid sarcoma is suspected, the differential diagnosis can be elucidated on immunohistochemical grounds. Early diagnosis provides the best opportunity for radical surgery at a stage when the tumour has not spread locally or disseminated systemically.

[The Balgrist Reference Center for Mesenchymal Tumors. The significance of a clinico-pathological tumor register]. / Das Balgrist Referenzzentrum für mesenchymale Tumoren. Die Bedeutung eines klinisch-pathologischen Tumorregisters.

Compared to other forms of cancer, malignant mesenchymal tumors are rare: individual surgeons see few such patients and do not usually treat them personally. The radiologic and histologic problems of differential diagnosis, and the subtle distinction between benign and malignant make decision an onerous task for surgeons, orthopedists, pathologists, oncologists and radiotherapists. For this reason referral centers should enable oncologic working groups to confirm diagnoses, establish appropriate therapeutic schedules, and to help in follow-up patient care. Around 1970, a center was created at Balgrist University Orthopedic Clinic for the gathering, documentation and coordination of clinical and pathological data from patients with tumors and tumorous lesions of the skeleton and soft tissues. Subsequently, a circle of continuously collaborating specialists, including some from other institutions, formed about the register. The viability of the reference center is assured by unequivocal morphologic diagnosis; presence of the pathologist during the planning and procedure of the biopsy and other tumor-related interventions in the operating room; clinical investigations including the immediate availability of diagnostic procedures; charting all clinical data; and the clinic's follow-up of its own patients. Fully integrated in the Orthopedic Clinic and Polyclinic, the register is a major instrument in the treatment of patients at risk with tumor. Given the diversity of clinicopathological presentation, the register permits direct access to analogous situations in individual cases.

[Benign fibrous histiocytoma of the distal femoral metaphysis. Differential diagnosis between neoplasm and growth disorder with identical morphology]. / "Benignes fibröses Histiozytom" der distalen Femurmetaphyse. Differentialdiagnose zwischen Neoplasie und Wachstumsstörung bei identischer Morphologie.

The typical radiologic finding of a "non-ossifying fibroma" of the distal femoral metaphysis was seen in a 17-year-old female patient with pain in the distal femur. The rapid development of this lesion was confirmed on the basis of earlier radiographs performed to clarify other complaints. Since the lesion had developed in no more than 34 months, with pronounced scintigraphic and MRI signal intensity, particularly in the late phase, and pain had prompted the patient to seek examination, the cause was assumed to be a neoplasia rather than a growth disorder. Histopathological examination revealed a proliferative fibrohistiocytic lesion which was histologically different from a malignant fibrous histiocytoma. The finding indicates that in the differential diagnosis between non-ossifying fibroma and benign fibrous histiocytoma in cases with identical localization, pain and the intensity of the scintigraphic signal may well be the key to further action: since benign fibrous histiocytomas may be regarded as genuine neoplasias, the question of malignancy should also be clarified beyond doubt.