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.

Residual lesions of cerebral fat embolism.

Necropsy findings of a case which survived for three months after massive cerebral fat embolism are presented. The lesions are characterized by numerous patchy necroses and areas of demyelination in the white matter of cerebral and cerebellar hemispheres and brain stem, accompanied by atrophy of white matter and ventricular enlargement. Attention is drawn to the significance of these lesions for posttraumatic coma or dementia.

Clinical experience with preoperative chemotherapy for osteosarcoma.

Since 1978 preoperative chemotherapy has been administered to 15 consecutive patients with osteosarcomas in Zurich. Preoperative chemotherapy was acceptably well tolerated and did not impair surgical procedures. Our retrospective analysis confirmed that the extent of necrosis after preoperative chemotherapy is of biological importance for the further course of the disease. Patients with extensive necrosis had better relapse-free survival and longer overall survival than those with little necrosis.

Primary intracranial germ-cell tumors. A clinicopathological study of 14 cases.

Fourteen cases of primary intracranial germ-cell tumors are presented. Histologically, there were eight germinomas, three teratomas, and three germ-cell tumors of more than one histological type. Immunohistochemical studies revealed alpha-fetoprotein in yolk-sac tumor components in two cases and beta human choriogonadotropin in syncytiotrophoblastic giant cells in one case. One teratoma contained an unusual pleomorphic sarcomatous portion with features of early myoblastic differentiation. Comparison of intracranial with gonadal germ-cell tumors shows that the same subtypes are found in both locations with comparable incidence and similar biological behavior. The detailed World Health Organization classification of testicular germ-cell tumors should be applied to the histopathological classification of intracranial germ-cell tumors. Despite the critical location of intracranial germ-cell tumors, a good outcome can be achieved by optimal surgical excision. A primary microsurgical approach provides a histopathological diagnosis, which is indispensable for the proper choice of postoperative management.

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.

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.

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.

[Suspicion of bone tumor: planning of the biopsy from the pathologist's viewpoint]. / Verdacht auf Knochentumor: die Planung der Biopsie aus der Sicht des Pathologen.

Suspicion of a neoplastic lesion of bone presents particular problems for both clinicians and pathologists. In most cases biopsy will be planned and should be performed as for a malignant lesion. The material obtained must be representative as well as qualitatively and quantitatively adequate. X-ray data, intraoperative findings, and histopathologic results constitute the three prime sources of information on which diagnosis and prognosis are based; these condition the therapeutic modalities which must be elaborated in each case by a multidisciplinary approach.

[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.

Mitotic count in seminomas--an unreliable criterion for distinguishing between classical and anaplastic types.

Testicular seminomas occur in various forms of which the classical, the spermatocytic, and that with syncytiotrophoblastic giant cells are distinctly defined. Anaplastic seminomas, however, are less clearly distinguished. Forty-five seminomas, 39 pure and 6 combined tumors, were examined from the perspective of the current definition that 3 or more mitoses per high power field (m/hpf) distinguish the anaplastic from the classical form. Our resultant yield of over 80% of "anaplastic" seminomas is clearly incompatible with general clinical experience, indicating that the arbitrary criterion of 3 m/hpf does not segregate anaplastic forms from neoplasms that are mitotically active but relatively non-aggressive. Moreover, the evidence indicates that mitotic activity does not adequately define a tumor form that is near the undifferentiated end of the spectrum which extends from "embryonal carcinoma" to the spermatocytic type. If it should prove, however, that the mitotic rate must be used as an arbitrary watershed criterion until a more reliable one is found, it should then be set at more than 5 m/hpf, yielding a percentage of anaplastic seminomas (about 9%) that is compatible with clinical experience.

Spontaneous necrosis in osteosarcomas.

In the treatment of osteosarcoma pre-operative chemotherapy has assumed considerable importance in helping improve survival, and enabling limb-sparing procedures. The quantitative assessment of tumour necrosis in the resected specimen by morphological means has become a significant step in judging therapeutic response and in helping determine post-operative management. Different systems of grading tumour regression have been proposed. Little is known, however, about the morphology or degree of spontaneous necrosis in osteosarcomas, in particular to what extent necrosis can be considered to be due to cytotoxic treatment. For this purpose, 13 osteosarcomas, taken from patients treated by surgery alone, were examined by the same method we routinely employ in assessing chemotherapeutic response. The results demonstrate that the extent of spontaneous necrosis does not approach that achieved in response to chemotherapy. Sub-total necrosis may be due to spontaneous regression, inadequate therapeutic response, or to a combination of both. Hence, only two categories of response, good and poor, appear relevant and these terms should be used in preference to good, intermediate and poor.

Pleomorphic adenoma of the human breast.

Pleomorphic adenomas of the human breast are histologically identical to those of salivary glands. To date, the literature reports but 15 such benign tumors, all of which occurred in women. The present paper describes clinical and pathologic findings in three further cases, including one man. Considered together, unnecessary mastectomy occurred in 44.4%, indicating the importance of separating this benign entity from malignancies with stromal metaplasia. In case of examination by frozen section, a peripheral portion, if not the entire tumor, should be submitted to the pathologist.

Primary osteosarcoma of the liver.

Extraskeletal osteosarcomas are infrequent, and those that arise within parenchymal organs are very rare indeed. This case of a 71-year-old man with a primary osteosarcoma of the liver is the second reported in man. Pathologic findings, including ultrastructural features, at surgery and autopsy are presented. The differential diagnosis is discussed in detail.

Chondroblastoma of the talus: natural development over 9.5 years. Case report.

The spontaneous development of chondroblastoma was seen clinically and demonstrated radiologically in the talus of a 5.5-year-old boy. It was followed for 9.5 years before surgery was performed. Histological examination revealed typical features. This suggests that chondroblastomas may undergo very slow growth and development. The case is compared with 31 other chondroblastomas of the foot.

Primary leiomyosarcoma of extragnathic bones. Case report and review of literature.

In a 60-year-old man, a swelling anteromedially just below the knee led to the discovery of an intraosseous leiomyosarcoma. It is the 13th documented case of primary leiomyosarcoma of bone outside the facial skeleton. Clinical and pathologic findings, modes of treatment and therapeutic results are reviewed, and theories of histogenesis discussed. As to the latter, ultrastructural features in our case support the pleuripotent mesenchymal rather than the vascular smooth muscle origin.

[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.

[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.