Pleomorphic spindle cell sarcoma (PSCS) formerly known as malignant fibrous histiocytoma (MFH): a complex malignant soft-tissue tumor.

A presentation defining the nature, characteristics, causation, treatment and outcome of patients with lesions formerly known as malignant fibrous histiocytoma and now as pleomorphic spindle cell sarcoma is clearly a very difficult subject. Many authors do not believe that the tumor exists and instead describe them as forms of fibrosarcomas, fibromyxoid lesions, dedifferentiated chondrosarcomas or even leiomyosarcomas. The reasons for this confusion are presumably related to the fact that the malignant pleomorphic spindle cell sarcoma does not seem to be a distinct type of lesion with specific histologic and genetic characteristics. Instead, the tumor has at least four separate histologic variations and no specific gene signature and in fact does not seem to be either familial or ethnic in presentation. In view of the fact that the tumor was traditionally the most frequently encountered malignant soft-tissue neoplasm, the world of orthopedic oncology is clearly distressed by the problems that these patients have and is joined by the radiation oncologists and chemotherapists in seeking new solutions.

Parallel DNA template preparation using a vacuum filtration sample transfer device.

Solid-phase techniques have facilitated the handling of biochemical analytes. This has stimulated the development of systems by which large sample panels can be analyzed with high levels of security and quality. We describe a sample transfer device based on the principle of vacuum filtration, which enables parallel handling of 96 samples of analytes bound to Sepharose beads. The tool was employed for strand separation of DNA samples, by attracting the beads to filter probes while passing them between the reagent solutions. The samples were analyzed using Pyrosequencing technology and proved to yield genotyping results of high quality. The presented sample preparation procedure provides an important link in the development of integrated systems for rapid genetic analysis at a low cost. In addition, the same filter could be reused extensively with very low risk for detectable cross-contamination between assays and without any reduction in processing capacity, thus further reducing the cost per analyzed sample.

Multiple hamartoma syndrome with osteosarcoma.

Multiple hamartoma syndrome, also known as Cowden's disease, is a rare genodermatosis with characteristic mucocutaneous lesions associated with multiple internal abnormalities. We describe a patient having classic dermatologic manifestations of Cowden's disease and multiple neoplasia including follicular adenocarcinoma of the thyroid gland with lung metastasis, intraductal breast carcinoma within a fibroadenoma, and an osteosarcoma. To our knowledge, this is the first reported case of an osteosarcoma in Cowden's disease.

Histological studies of the glenoid labrum from fetal life to old age.

To help to resolve the controversy regarding the composition of the glenoid labrum, thirty-eight shoulders from cadavera were examined grossly and histologically. We used specimens for individuals of different ages so that we could determine what changes occur as a result of aging. In children and adults, the labrum appeared to be fibrocartilaginous tissue. The labrum was a separate anatomical structure that could be distinguished from the fibrous capsule of the shoulder. Neonatal labra were composed of primitive mesenchymal tissue containing only few chondrocytes that modulated into fibrocartilage in the first few years of life. Neonatal labra contained no elastin, whereas specimens from adults had rare elastin fibers. The labrum was sparsely vascularized throughout its substance, with no particular pattern of distribution. Vascularity decreased with increasing age of the individual.

An investigation of a compliant interface for press-fit joint replacement.

Earlier in vitro studies showed that a compliant layer between a metal surface and trabecular bone improved the load distribution. In this study, the behavior of a compliant layer of Dacron velour was investigated in vivo using a patella resurfacing in a sheep as a model. Bilateral cases were used to compare the velour interface with a direct metal-to-bone interface. For the metal patellas, a fibrous layer developed adjacent to the metal while the underlying bone formed a new subchondral-like layer. With the velour interface, fibrous tissue invaded the velour, followed later by bone, which sometimes reached the metal surface. For follow-ups of 8 months or more, the load across the interface was transferred over localised patches, for both the press-fit and velour interfaces. There was no significant difference in the areas of contact. There was evidence that this was due to the irregularity of the bony surface beneath the fibrous layer, or to bone nodules actually growing up to the metal. It was concluded that in this in vivo model, the velour layer did not retain a more uniform load distribution compared with the press-fit joint, due to the nature of the bone and fibrous tissue that formed at the interfaces.

The use of flow cytometry as a diagnostic aid in the management of soft-tissue tumors.

The diagnosis and staging of soft-tissue tumors is a complex problem, and even the experienced pathologist sometimes finds it difficult to determine whether a particular lesion is benign or malignant and whether a sarcoma is high or low grade. However, this information is essential in planning treatment. Flow cytometric analysis of nuclear DNA is a method to determine the number of cells that are in the process of replicating or dividing (S or G2, or M phase), since these cells have abnormal concentrations of DNA (DNA aneuploidy). Previous studies from our laboratory have established the relative value of this technique as an adjunct in the staging of primary bone tumors. In the past four years, 146 soft-tissue lesions have been evaluated by flow cytometry, using propidium iodide staining of isolated cells that were obtained in the fresh state. The tumors were forty-two benign neoplasms, ten lesions of synovial origin, thirty desmoids (aggressive but not malignant), and sixty-four sarcomas ranging in grade from 1 to 3 on a 3-point scale. The over-all values for flow cytometry showed that a number of factors correlated well with the grade of the tumor, but the best correlations were with the mean concentration of DNA (a calculated average for concentrations of DNA for the various types of cells in the lesion), the total percentage of cells in S-phase plus the G2 and M-phases (called percentage of replicating and dividing cells), and the presence or absence of DNA aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible role of capillary action in pathogenesis of experimental catheter-associated dermal tunnel infections.

An animal model of vascular-catheter-associated dermal tunnel infections was developed to study the pathogenesis of such infections. Bacteria inoculated onto entry sites of catheters into skin could be identified by culture and Gram stain on the tips of plastic catheters (4 cm from the entry site) within 1 h of inoculation, whether the animal was inoculated at the time of insertion of the catheter or 1 week afterwards. Histological examination of dermal tunnels revealed that the introduction of bacteria preceded the development of tissue inflammation. Bacteria on entry sites of percutaneous catheters moved rapidly from the entry site into the dermal tunnel along the external catheter surface, perhaps suspended in a fluid phase and propelled by capillary action.

The histologic response of soft tissue sarcoma to radiation therapy.

Twenty-seven patients with soft tissue sarcoma had preoperative radiotherapy, limb-sparing marginal surgical resection and whole-mount tumor histologic analysis. Incisional biopsy specimens before radiotherapy were reviewed for tumor type, grade, and extent of necrosis. Preoperative radiotherapy was given in either of two regimens: 13 patients received a mean total dose of 5250 cGy in one daily 180 to 200 cGy fractions and 14 patients a mean total dose of 4770 cGy in two daily fractions of 180 to 200 cGy separated by 4 hours. Twenty-one specimens had at least 80% necrosis or severely altered cells, a 3+ to 4+ response. Grade and size of the tumor appeared to be indicators of response to treatment rather than histologic type. Three of five patients (60%) with Grade 1, eight of 11 patients (73%) with Grade 2 lesions, and ten of 11 patients (91%) with Grade 3 tumors had 80% or greater necrosis or severely altered cells. For tumors 10 cm or less in greatest diameter, the 3+ to 4+ histologic response was seen in 12 of 14 patients (86%) whereas for lesions greater than 10 cm, this response was observed in nine of 13 patients (69%). For patients with Grade 2 or 3 soft tissue sarcoma, 13 of 14 patients (93%) treated with two fractions per day and two of four patients (50%) receiving one fraction per day exhibited significant response. All six patients treated twice daily for lesions greater than 10 cm had 3+ to 4+ histologic response compared to three of seven (43%) patients treated once per day. Therefore, grade and size of soft tissue sarcoma are important predictors of response to radiotherapy and preoperative twice daily radiotherapy may more likely permit the conservative surgical excision of sarcomas of borderline resectability.

Soft tissue sarcomas of the hand.

The most common soft tissue sarcomas of the hand are epithelioid sarcoma, rhabdomyosarcoma, synovial sarcoma, fibrosarcoma, and clear cell sarcoma. The epidemiology and biology of these tumors are discussed and important unifying concepts, such as local recurrences and regional lymph node metastases, are stressed.

Vascular events associated with the appearance of the secondary center of ossification in the murine distal femoral epiphysis.

Although the formation of a secondary center of ossification is often compared with that of the primary center, there are striking differences between these processes. In the formation of the primary center, vascular invasion is always associated with the maturation of chondrocytes, whereas vascularization of the epiphysis can proceed in two different ways. In some species, the epiphysis is vascularized by cartilage canals before the appearance of the secondary center. However, in the mouse, the distal femoral epiphysis is vascularized by peripheral vascular invasion without pre-existing cartilage canals. Histological study of serial sections and studies of vascularization by injection with India ink demonstrated the relationship between hypertrophic chondrocyte formation, vascular invasion, and the formation of the secondary center of ossification in the murine distal femoral epiphysis.

Chondrosarcoma of the temporal bone. Diagnosis and treatment of 13 cases and review of the literature.

Chondrosarcoma of the temporal bone is a rare lesion. Clinically it has been confused with multiple sclerosis, glomus jugulare tumors, meningioma, and chordomas. The cranial nerve palsies frequently observed with the tumors are related to the anatomic locations of the tumors. Thirteen patients with this entity are presented and the eleven other cases in the literature are reviewed. Histologically the tumors are low grade and exhibit myxoid features. The myxoid features must be differentiated from chordoma and chondroid chordoma. The tumor locations preclude surgical excision and conventional radiation therapy can cause unacceptable neurologic sequelae. Proton beam therapy has been effective in short-term results and appears capable of avoiding serious neurologic side effects.

Localized osteolysis in stable, non-septic total hip replacement.

We are reporting four cases of extensive, localized bone resorption adjacent to a rigidly anchored, cemented total hip replacement. None of these hips showed evidence of infection on clinical, bacteriological, or pathological evaluation. The tissue from the regions of osteolysis showed sheets of macrophages and foreign-body giant cells invading the femoral cortices. Abundant methylmethacrylate particulate debris was present in the tissues, but polyethylene wear debris was absent. The histological appearance of this tissue resembled that reported about loosened total hip implants with the exception of the synovial-like layer at the cement surface. The cases reported here show that aggressive bone lysis may occur around stable cemented total hip arthroplasties without the presence of sepsis or malignant disease.

Characterization of cells from human giant cell tumors of bone.

In vitro cell culture techniques were used to identify and characterize the individual cell types present in human giant cell tumors of bone. Three major cell types were identified based on morphologic characteristics, patterns of specific cell surface antigens, presence of receptors for hormones, and cell products. One population consisted of mononuclear cells that expressed monocyte-macrophage markers. These cells lacked receptors for skeletal hormones and did not persist in culture. Distinct from these cells was a population of mononuclear cells that proliferated in culture and most likely represented the neoplastic element of the tumor. These cells phenotypically resembled connective tissue stromal cells, i. e., they did not express macrophage surface antigens and they produced collagens (Types I and III). They also possessed receptors for parathyroid hormone. The final population of tumor cells consisted of multinucleated giant cells. These cells lacked monocyte-macrophage surface antigens and possessed receptors for calcitonin, a phenotypic marker for osteoclasts. These studies illustrate that in vitro cell culture techniques can be employed to identify and characterize the cell populations of tumors of skeletal tissues, and demonstrate the usefulness of these cell culture models for investigating the biology of bone tumors.

Extraosseous osteosarcoma presenting with intestinal hemorrhage: case report and literature review.

A 23-year-old man presented with intestinal bleeding due to an extraosseous osteosarcoma of the jejunum. A lesion was also found in the deltoid muscle, and other metachronous soft tissue sites developed subsequently. The presence of malignant osteoid was documented by immunohistochemical studies of one of the lesions. The patient died of metastatic disease 19 months after diagnosis, despite surgical resections and adjuvant chemotherapy. This unique presentation is discussed, and the literature concerning extraosseous osteosarcoma is reviewed.

Detection and developmental changes of the 1,25-(OH)2-D3 receptor concentration in mouse skin and intestine.

We investigated [3H]1,25-dihydroxyvitamin D3-specific binding activity in fetal, neonatal, and adult mouse skin to determine (a) during which stage in development the skin develops the capacity to respond to this hormone and (b) whether the hormone binding activity changed during development and maturation. A macromolecule with properties similar to those of the chick intestinal 1,25-dihydroxyvitamin D3 receptor was detected in the skin and intestine of mouse pups at 17 days of fetal life. 1,25-Dihydroxyvitamin D3-specific binding activity from both tissues sedimented on linear sucrose gradients at 3.5-3.7S and eluted from DNA cellulose at 0.22 M KCl. At earlier stages of fetal life (12-14 days) receptor-like activity was detected in cytosols prepared from whole-mouse fetuses. 1,25-Dihydroxyvitamin D3-specific binding activity was quantitated in the skin and intestine throughout development using a chromatin binding assay. Scatchard analysis of saturation binding data showed that the concentration of binding activity in skin increased rapidly after birth and reached a maximum when the mice were 10-19 days old. By contrast, the binding activity that was detected in the fetal and neonatal whole intestine remained low until the mice were weaned. The affinity (Kd) of the binding activity was similar in skin and intestine at all ages studied. It is concluded that 1,25-dihydroxyvitamin D3-specific binding activity appears in both skin and intestine of the mouse prior to birth and increases in these two tissues during different stages in development.

Desmoplastic fibroma of bone. A report of eight cases and review of the literature.

Desmoplastic fibroma of bone is a rare benign tumor consisting of thin, wavy fibroblasts set in an abundant matrix of collagen fibers. At times it is difficult to distinguish desmoplastic fibroma from other fibrous lesions, especially low-grade fibrosarcomas. Fewer than eight cases have been previously reported. We have reviewed the diagnostic and therapeutic findings of eighty additional cases. Six patients had the lesions located in an extremity and two had an axial lesion. The average age of the patients was twenty-five years (range, twelve to fifty-six years) and all of the patients had more than two years of follow-up (range, two to seventeen years). The radiographic findings in all but one patient were of a purely lytic, honeycombed lesion that often widened the bone, and was metaphyseal in long bones. The tumor replaced the medullary cavity with a grayish-white, rubbery to firm tissue that was often, but not always, contained by a rim of periosteal reactive bone. Histologically, the features were: (1) prominent loose bundles of fibrous tissue composed of slim, spindle-shaped fibroblasts with wavy, elongated nuclei; (2) variable amounts of bands of collagen fibers; and (3) absence of mitoses or atypical cells. Areas of metaplastic bone were found only around sites, of pathological fractures. The biology of desmoplastic fibroma is different from that of other benign fibrous lesions in that the lesion is very destructive locally and often recurs after incomplete excision. It is also distinguished from low-grade malignant lesions (for example, fibrosarcoma) in that metastases have never been reported. In our series an intralesional excision was initially performed in six of the eight patients and a marginal resection, in two. There were four recurrences, treated by a marginal resection in two patients and repeat curettage in one. The recurrence in the fourth patient required an amputation above the knee after two additional intralesional procedures had been unsuccessful. Wide or marginal resection appears to be the treatment of choice when the lesion is located in a site that can be resected without significant loss of function. In other areas, an attempt at curettage, instillation of phenol, and bone-grafting seems to be warranted, resorting to more radical procedures only if this fails to control local disease.

Grading of bone tumors by analysis of nuclear DNA content using flow cytometry.

We studied 217 consecutive tumors of bone by flow cytometric analysis of nuclear DNA concentration after staining with propidium iodide. A diagnosis and histological grade (benign, low-grade, or high-grade sarcoma) were assigned to each tumor on the basis of staging data (with the exception of the forty-six giant-cell tumors, which, although indistinguishable histologically, were divided according to the flow cytometric pattern into two distinct groups), and we quantitatively studied the flow cytometry data to assess the percentages of cells in diploidy, tetraploidy, or aneuploidy. When compared, the mean values for the flow cytometric data for the three grades showed significant differences. Criteria were established for the three classes of tumors: for benign tumors, less than 11 per cent tetraploidy and no aneuploidy; for low-grade sarcomas, more than 11 per cent and less than 17 per cent tetraploidy, and no aneuploidy; and for high-grade tumors, either more than 17 per cent tetraploidy or aneuploidy. Tests for compliance for all groups of tumors (excluding the forty-six giant-cell tumors)--benign, low grade, or high grade--were significant for most of the benign lesions (with the exception of chondroblastoma and fibrous dysplasia) and for the high-grade sarcomas (with the exception of round-cell tumors). The low-grade sarcomas did far less well, based principally on the failure of the low-grade chondrosarcomas, chordomas, and adamantinomas to comply with the criteria. An attempt to assess the value of the system as a predictor of metastases showed that a low percentage of diploid cells (less than 75 per cent) and the presence of an aneuploid peak correlated statistically with the development of metastatic disease, but the usefulness of this observation could not be fully assessed because of multiple variables, associated principally with treatment.

Diagnosis of borderline cartilage lesions of bone.

Cartilage lesions of bone are the most difficult ones for the pathologist to classify. The reasons for this are discussed. The borderline cartilage lesions include osteochondroma, enchondroma, chondrosarcoma, chondroblastoma, chondromyxoid fibroma, juxtacortical chondroma and chondrosarcoma, clear cell chondrosarcoma, and the peripheral chondrosarcoma. Specific differential points are provided with illustrative material and a summary table in order to ease the pathologist's task.