[Histopathological classification principles of rheumatic joint diseases : Contribution of pathology to the diagnosis]. / Histopathologische Klassifikationsprinzipien rheumatischer Gelenkerkrankungen : Beitrag der Pathologie zur Diagnose.

Even though the diagnostics of rheumatic joint diseases are mostly based on clinical, immunoserological and imaging criteria, histopathology can also make a significant contribution. This is particularly true for clinically unclear monoarticular and periarticular diseases. The contribution of histopathology to the diagnosis of rheumatic diseases is manifold since the histopathological differential diagnosis includes the complete spectrum of synovial diseases. This heterogeneous pathogenetic spectrum is described in the joint pathology algorithm, which includes inflammatory and non-inflammatory diseases. To the latter group belong certain benign tumors such as the diffuse variant of the tenosynovial giant cell tumor, lipoma, hemangioma, vascular malformations and synovial chondromatosis. Additionally, the rare group of storage diseases should be kept in mind. Inflammatory diseases can be discriminated into crystal-induced arthropathies mainly such as gout and pseudogout, into granulomatous diseases such as tuberculosis and foreign-body inoculations, and finally into the large group of non-granulomatous, non-infectious synovitis. This large group is by far the most common, and it often causes difficulties in assigning the histopathological findings to a concrete rheumatologic diagnosis. In this context the synovitis score should be applied as a diagnostic device in these cases, leading to the diagnosis of a low-grade synovitis (which is associated with degenerative arthropathies) or of a high-grade synovitis (associated with rheumatic diseases). Identification of crystals and crystal-like deposits should be carried out with the application of the joint particle algorithm which addresses the identification of endogenous and non-endogenous particle deposits in the synovial tissues. Additionally, the synovitis-score may be used for evaluation of arthritis-progresssion and for the evaluation of inflammation-regression as a consequence of therapy with biologicals.

Diagnostic guidelines for the histological particle algorithm in the periprosthetic neo-synovial tissue.

BACKGROUND: The identification of implant wear particles and non-implant related particles and the characterization of the inflammatory responses in the periprosthetic neo-synovial membrane, bone, and the synovial-like interface membrane (SLIM) play an important role for the evaluation of clinical outcome, correlation with radiological and implant retrieval studies, and understanding of the biological pathways contributing to implant failures in joint arthroplasty. The purpose of this study is to present a comprehensive histological particle algorithm (HPA) as a practical guide to particle identification at routine light microscopy examination. METHODS: The cases used for particle analysis were selected retrospectively from the archives of two institutions and were representative of the implant wear and non-implant related particle spectrum. All particle categories were described according to their size, shape, colour and properties observed at light microscopy, under polarized light, and after histochemical stains when necessary. A unified range of particle size, defined as a measure of length only, is proposed for the wear particles with five classes for polyethylene (PE) particles and four classes for conventional and corrosion metallic particles and ceramic particles. RESULTS: All implant wear and non-implant related particles were described and illustrated in detail by category. A particle scoring system for the periprosthetic tissue/SLIM is proposed as follows: 1) Wear particle identification at light microscopy with a two-step analysis at low (× 25, × 40, and × 100) and high magnification (× 200 and × 400); 2) Identification of the predominant wear particle type with size determination; 3) The presence of non-implant related endogenous and/or foreign particles. A guide for a comprehensive pathology report is also provided with sections for macroscopic and microscopic description, and diagnosis. CONCLUSIONS: The HPA should be considered a standard for the histological analysis of periprosthetic neo-synovial membrane, bone, and SLIM. It provides a basic, standardized tool for the identification of implant wear and non-implant related particles at routine light microscopy examination and aims at reducing intra-observer and inter-observer variability to provide a common platform for multicentric implant retrieval/radiological/histological studies and valuable data for the risk assessment of implant performance for regional and national implant registries and government agencies.

15 years of the histopathological synovitis score, further development and review: A diagnostic score for rheumatology and orthopaedics.

The histopathological synovitis score evaluates the immunological and inflammatory changes of synovitis in a graduated manner generally customary for diagnostic histopathological scores. The score results from semiquantitative evaluation of the width of the synovial surface cell layer, the cell density of the stroma and the density of the inflammatory infiltration into 4 semiquantitative levels (normal 0, mild 1, moderate 2, severe 3). The addition of these values results in a final score of 0-9 out of 9. On the basis of this summation the condition is divided into low-grade synovitis and high-grade synovitis: A synovitis score of 1 to≤4 is called low-grade synovitis (arthrosis-associated/OA synovitis, posttraumatic synovitis, meniscopathy-associated synovitis and synovitis with haemochromatosis). A synovitis score of≥5 to 9 is called high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme arthritis, postinfection/reactive arthritis and peripheral arthritis with Bechterew's disease). By means of the synovitis score it is therefore possible to distinguish between degenerative/posttraumatic diseases (low-grade synovitis) and inflammatory rheumatic diseases (high-grade synovitis) with a sensitivity of 61.7% and a specificity of 96.1%. The diagnostic accuracy according to ROC analysis (AUC: 0.8-0.9) is good. Since the first publication (2002) and an associated subsequent publication (2006), the synovitis score has nationally and internationally been accepted for histopathological assessment of the synovitis. In a PubMed data analysis (status: 14.02.2017), the following citation rates according to Cited by PubMed Central articles resulted for the two synovitis score publications: For DOI: 10.1078/0344-0338-5710261 there were 29 Cited by PubMed Central articles and for the second extended publication DOI:10.1111/j.1365-2559.2006.02508 there were 44 Cited by PubMed Central articles. Therefore a total of 73 PubMed citations are observed over a period of 15 years, which demonstrates an international acceptance of the score. This synovitis score provides for the first time a diagnostic, standardised and reproducible histopathological evaluation method enabling a contribution to the differential diagnosis of chronic inflammatory general joint diseases. This is particularly the case by incorporation into the joint pathology algorithm. To specify the synovitis score an immunohistochemical determination of various inflammation-relevant CD antigens is proposed to enable a risk stratification of high-grade synovitis (e.g.: progression risk and sensitivity for biologicals).

[Fifteen years of the histopathological synovitis score : Review and further developments of a diagnostic score]. / 15 Jahre histopathologischer Synovialitis-Score : Rückblick und Weiterentwicklung eines diagnostischen Scores.

The histopathological synovitis score evaluates in a graded approach, as is largely usual for diagnostic histopathological scores, the immunological and inflammatory changes caused by synovitis. A synovitis score of between 1 and ≤ 4 is classified as low-grade (osteoarthritis-related synovitis, post-traumatic synovitis, meniscopathy-related synovitis and synovitis in hemochromatosis). Synovitis scores of between ≥ 5 and 9 are classified as high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme's arthritis, post-infection/reactive arthritis and peripheral arthritis in Bechterew disease); sensitivity is 61.7% and sensitivity 96.1%. According to receiver operating characteristic (ROC) analysis (AUC: 0.8-0.9), diagnostic value is good. National and international acceptance of the synovitis score has grown since the first publication in 2002 and a related follow-up publication in 2006. PubMed data analysis (as of 11.01.2017) yielded the following citation values according to "cited by PubMed Central articles" for two publications relating to the synovitis score: there were 29 cited-by-PubMed articles for DOI: 10.1078/0344-0338-5710261 , and 44 cited-in-PubMed articles for the second publication, DOI: 10.1111/j.1365-2559.2006.02508 . This makes a total of 73 PubMed citations over a period of 15 years, thereby evidencing the score's international acceptance. Immunohistochemical determination of a number of CD antigens relevant to inflammation has been proposed to further specify the synovitis score for the purposes of risk stratification of high-grade synovitis (e.g., risk of progression and sensitivity to biological agents).

[Histopathological diagnostic work-up of joint endoprosthesis-associated pathologies]. / Histopathologische Diagnostik von Gelenkendoprothesen-assoziierten Erkrankungen.

Increasing classes of joint implants and the combination of materials results in increased and wear-associated pathologies. According to the revised consensus classification, the following types can be recognized at conventional histological examination: Type I, particle-induced type; Type II, infection type; Type III, combination type; Type IV, indifferent type; Type V arthrofibrotic type; Type VI, allergic/immunological/toxic adverse reactions and Type VII, bone pathologies. Wear particles are histopathologically characterized according to the Krenn particle algorithm which focuses on a descriptive identification of wear particles and the differentiation of other nonwear-related particles. Type VII is considered histologically when there is evidence of a perivascular/interstitial lymphocytic CD20- and CD3-positive infiltrate, presence of mast cells and eosinophils, and tissue necrosis/infarction associated with implant wear material. Since wear particle-induced toxicity cannot be differentiated with certainty from hypersensitivity/allergic reaction on histological examination, immunological-allergological and clinical data should be used as supplementary criteria for the differential diagnosis. Tissue sampling should be performed from periprosthetic soft tissue with location mapping and when feasible also from bone tissue. Additional information regarding the type of implant and clinical, radiological, immunological, and microbiology data should be available to the pathologist. Further immunohistochemical studies are recommended in the following settings: infection (CD15, CD20, CD68); prosthesis-associated arthrofibrosis (ß­catenin); allergic/immunologic/toxic adverse reactions (CD20, CD3, CD4, CD8, CD117 and for T­cell characterization T­bet, GATA-3, and FOXP3).

Revised histopathological consensus classification of joint implant related pathology.

This extended classification of joint implant related pathology is a practical histopathologic classification based on defined morphological criteria covering the complete spectrum of pathohistologic changes in periprosthetic tissues. These changes may occur as a consequence of endoprosthetic replacement of large joints and may lead to a reduction in the prosthesis survival rate. We describe the established consensus classification of the periprosthetic membrane, in which aseptic and septic prosthetic loosening can be subdivided into four histological types, as well as histopathological criteria for additional significant pathologies including endoprosthetic-associated arthrofibrosis, particle-induced immunological, inflammatory and toxic mechanisms (adverse reactions), and bone tissue pathologies. These characteristic tissue alterations and their relationships are summarized in the extended classification. Since particle heterogeneity in periprosthetic tissue is high and particle identification is a necessary part of diagnosis, the identification of different types of particles is described in the histopathological particle algorithm. The morphological qualities of prosthetic material particles and the demarcation between abrasion and non-abrasion endogenous particles are also summarized. This feasible classification which is based on low cost standard tissue processing and examination and on well-defined diagnostic criteria is a solid platform for the histological diagnosis of implant associated pathologies providing a stable and reproducible tool for the surgical pathologist. Since this classification is suitable for standardized histopathological diagnostics, it might also provide a useful data set for joint arthroplasty registers, particularly for registers based on so-called routine data.

[Histopathological particle algorithm. Particle identification in the synovia and the SLIM]. / Histopathologischer Partikelalgorithmus. Partikelidentifikation in der Synovialis und in der SLIM.

BACKGROUND: In the histopathological diagnostics of synovitis and the synovium-like interface membrane (SLIM) the identification of crystals and crystal-like deposits and the associated inflammatory reactions play an important role. The multitude of endogenous crystals, the range of implant materials and material combinations, and the variability in the formation process of different particles explain the high morphological particle heterogeneity which complicates the diagnostic identification of diagnostic particles. STUDY DESIGN AND METHODS: A simple histopathological particle algorithm has been designed which allows methodological particle identification based on (1) conventional transmitted light microscopy with a guide to particle size, shape and color, (2) optical polarization criteria and (3) enzyme histochemical properties (oil red staining and Prussian blue reaction). These methods, the importance for particle identification and the differential diagnostics from non-prosthetic materials are summarized in the so-called histopathological particle algorithm. RESULTS: A total of 35 cases of synovitis and SLIM were analyzed and validated according to these criteria. Based on these criteria and a dichotomous differentiation the complete spectrum of particles in the SLIM and synovia can be defined histopathologically. CONCLUSION: For histopathological diagnosis a particle score for synovitis and SLIM is recommended to evaluate (1) the predominant type of prothetic wear debris with differentiation between microparticles, and macroparticles, (2) the presence of non-prosthesis material particles and (3) the quantification of particle-association necrosis and lymphocytosis. An open, continuously updated web-based particle algorithm would be helpful to address the issue of particle heterogeneity and include all new particle materials generated in a rapidly changing field.

Salmonella septic arthritis of the knees in a patient with systemic lupus erythematosus.

Hematogenous Salmonella osteomyelitis is uncommon in immunocompetent hosts, but occurs with some regularity in immunosuppressed patients affected by systemic lupus erythematosus (SLE). Surgical debridement with resection of compromised tissue is central to the surgical management of osteomyelitis. Persistence of septic arthropathy may result from inadequate debridement, areas of osteonecrosis (ON), and an abnormal cellular and humoral dysregulation characteristic of SLE. We describe a 53-year-old Hispanic female with SLE on immunosuppressive therapy, who developed acute salmonella-induced septic arthritis and osteomyelitis of both knees associated with ON and recurrent SLE synovitis. She received prolonged antibiotic therapy and an extensive surgical debridement as part of a successful two-stage bilateral total knee replacement. This report illustrates the significance of Salmonella enterica infection in SLE patients, and the role of underlying bone and joint pathology such as bone infarcts, sub-acute osteomyelitis, and SLE synovitis.

[Revised consensus classification. Histopathological classification of diseases associated with joint endoprostheses]. / Erweiterte Konsensusklassifikation. Histopathologische Klassifikation von Gelenkendoprothesen-assoziierten Erkrankungen.

The revised classification of the periprosthetic membrane (synovial-like interface membrane SLIM) encompasses all pathological alterations which can occur as a result of endoprosthetic replacement of major joints and lead to a reduction in durability of prostheses. This also includes the established consensus classification of SLIM by which aseptic and septic prosthetic loosening can be subdivided into four histological types and histopathological criteria for additional pathologies: endoprosthesis-associated arthrofibrosis, immunological/allergic alterations and osseous pathologies. This revision represents the foundation for the histopathological diagnostics of the total spectrum of diseases associated with joint prostheses, is a suitable basis for a standardized diagnostic procedure and etiological clarification of endoprosthesis failure and also as a data standard for endprosthesis registers, in particular for registers based on routine data (e.g. German endoprosthesis register).

Acute inflammation with induction of anaphylatoxin C5a and terminal complement complex C5b-9 associated with multiple intra-articular injections of hylan G-F 20: a case report.

OBJECTIVE: The purpose of this case report was to investigate local immune mechanisms present during an acute inflammatory flare initiated by viscosupplementation with hylan G-F 20 in a patient with osteoarthritis (OA) and past meniscectomy. EXPERIMENTAL DESIGN: A patient with a history of bilateral OA and partial left knee meniscectomy, who had received three injections of hylan G-F 20, was diagnosed with an acute flare reaction in the left knee. Her chart was evaluated for clinical, radiological, and laboratory findings and for clinical follow-up. Histopathological synovial examination and real-time polymerase chain reaction (RT-PCR) for genes with major roles in local inflammation and enzyme-linked immunosorbent assays (ELISAs) for markers of complement activation and cytokines were performed. To study the impact of the inflammatory and immune features we compared the case patient with groups of three representative OA and three rheumatoid arthritis (RA) patients. RESULTS: The patient exhibited evidence of highly increased acute phase reactant C-reactive protein (CRP) in the blood. The pathological examination of the synovial membrane identified abundant fibrinous exudate with numerous particles of hyaluronan surrounded by a dense infiltrate of neutrophils and eosinophils. The synovium had moderate hypertrophy and sclerosis as well as an inflammatory infiltrate predominantly composed of T lymphocytes and macrophages with scattered perivascular eosinophils and neutrophils. Immunoperoxidase staining identified numerous deposits of C5b-9 in the fibrinous exudates and the synovial membrane of the patient. Similar findings were observed in the RA patients, whereas deposits were rare in OA synovial samples. In addition, both anaphylatoxin C5a and the terminal complement complex C5b-9 were present at high levels, comparable to those in RA patients. The levels of mRNA for interleukin-1 beta (IL-1ß), IL-6, and the neutrophil marker myeloperoxidase (MPO) were markedly increased compared to those in the RA and OA patients. CONCLUSIONS: This present study is indicative of a pseudo-septic acute inflammatory reaction in response to local accumulation of hylan G-F 20 with the activation of complement and local invasion of pro-inflammatory cells.

BMP signaling components are expressed in human fracture callus.

Of the various growth factors involved in the healing response after a fracture, bone morphogenetic proteins (BMPs) are emerging as key modulators. BMPs exert their effects by binding to a complex of type I and type II receptors leading to the phosphorylation of specific downstream effector proteins called Smads. The current study examined the presence of BMP signaling components in human callus obtained from five nascent malunions undergoing fracture fixation. These callus samples represented various stages of bone healing and a mixture of endochondral and intramembraneous bone healing. We performed immunohistochemistry on the callus, using antibodies for BMP (BMP-2,-3,-4,-7), their receptors (BMPR-IA, -IB, -II), and phosphorylated BMP receptor-regulated Smads (pBMP-R-Smads). Active osteoblasts showed fairly consistent positive staining for all BMPs that were examined, with the immunoreactivity most intense for BMP-7 and BMP-3. Immunostaining for BMPs in osteoblasts appeared to colocalize with the expression of BMPR-IA, -IB, and -II. Positive immunostaining for pBMP-R-Smads suggests that the BMP receptors expressed in these cells are activated. Staining for BMPs in cartilage cells was variable. The immunostaining appeared stronger in more mature cells, whereas staining for BMP receptors in cartilage cells was less ubiquitous. However, the expression of pBMP-R-Smads in cartilage cells suggests active signal transduction. Fibroblast-like cells also had a variable staining pattern. Overall, our findings indicate the presence of BMPs, their various receptors, and activated forms of receptor-regulated Smads in human fracture callus. To the best of our knowledge, this is the first study that documents the expression of these proteins in human fracture tissue. Complete elucidation of the roles of BMP in bone formation will hopefully lead to improved fracture healing care.

[Analysis of cause of death in the 1st and last periods of the Piedmontese Dialysis and Transplantation Registry]. / Analisi delle cause di morte nel primo e nell'ultimo periodo del Registro Piemontese di Dialisi e Trapianto (RPDT).

The aim of this study is to assess the mortality causes in dialysis in the Piedmont Region, using the data of the Dialysis and Transplantation Register (DTR). Data of a 15-year use of the DTR regarding 5519 hospital dialysis admissions were considered. Mortality seems to be particularly due to cardiac causes analyzing, also the incidence of other causes of death such as: cachexia, sudden death and infection causes.

Sarcoma in association with bone infarcts. Report of five cases.

Sarcoma associated with bone infarct is rare, and only 41 well-documented cases have been published. We describe five additional patients, three women and two men, aged 39 to 57 years. The tumors involved the femur (three patients), tibia (one patient), and humerus (one patient). In three patients, the infarcts were idiopathic. Radiologic evidence of malignancy was found in all patients, and bone infarcts were suspected in four. Four of the patients had malignant fibrous histiocytoma and one an osteosarcoma. Histologically, bone infarcts were seen in all patients, but in three they were mostly replaced by tumor. Portions of intact infarcts were seen adjacent to the tumor, indicating that they had preceded the development of the sarcoma. No hypercellular or atypical reparative tissue was found in the infarcted bones or in three additional uncomplicated infarcts studied from the same patients. The pathogenesis of sarcoma arising in bone infarct is unknown. The prognosis is poor; four of our five patients died within 2 years.

[Patients with neoplastic disease or older than 80 years of age: dialysis survival]. / Pazienti con patologia neoplastica o di età superiore ad 80 anni: destino dialitico.

In several European countries, including Italy, the resident population is ageing. This process is at the basis of the progressive increase in incidence of new elderly patients starting dialysis and, to a lesser degree, of patients affected by severe comorbid conditions, such a neoplasia. The aim of the study was an analysis of the situation in Piedmont (Northern Italy, 4,400,000 inhabitants): out of 4483 new entries in 1981-1993, 192 were aged 80 years and 87 were affected by renal neoplasia or by multiple myeloma. Incidence of patients aged 80 increased throughout the period; use of high tolerance techniques increased in the meantime allowing an improvement in survival results. The high incidence of vasculopathic patients and the high rates of death from cachexia pinpoint how much still has to be done in the field of prevention, even before dialysis starts.

Malignant mesenchymoma.

BACKGROUND: Malignant mesenchymomas are rare soft tissue tumors that contain two or more distinct histologic subtypes of sarcoma within the same tumor (exclusive of a fibrosarcomatous or hemangiopericytomatous component). They are generally considered high grade neoplasms and are associated with a poor prognosis, although experience with these tumors is limited. METHODS: We report 8 patients seen at our center over the last 22 years and describe the clinical course of a patient with a malignant mesenchymoma arising in the retroperitoneum whose experience typifies the aggressive behavior of this tumor. RESULTS: All eight patients had large, high grade tumors located in the retroperitoneum or thigh. Six of the 8 died of disease and 2 were alive with disease at a median of 30 months from diagnosis. CONCLUSIONS: Malignant mesenchymoma represents a particularly aggressive form of soft tissue sarcoma. Our experience with this disease highlights the need for more effective treatment strategies for these patients.

Resection of brain metastases from sarcoma.

BACKGROUND: Brain metastases from sarcoma are rare, and data concerning the treatment and results of therapy are sparse. METHODS: We retrospectively reviewed 25 patients with brain metastases from sarcoma of skeletal or soft-tissue origin, surgically treated in a single institution during 20 years. RESULTS: In 18 patients the brain lesion was located supratentorially, and in 7 patients infratentorially. Median age at brain metastasis diagnosis was 25 years. Median time from primary diagnosis to diagnosis of brain metastasis was 26.7 months. Lung metastases were present in 19 patients and in 8 patients they were synchronous with the brain lesion. Pulmonary metastases were resected in 12 patients (48% of total, and 63% of those with pulmonary lesions). The overall median survival from diagnosis of the primary sarcoma was 38 months and from craniotomy was 7 months. The presence or absence of lung lesions did not alter the median survival as calculated from diagnosis of brain metastasis. Overall percent survival was 40% at 1 year and 16% at 2 years. CONCLUSIONS: Because brain metastases from sarcoma are refractory to alternative treatment, surgical excision is indicated when feasible. Brain metastases from sarcoma are uncommon, usually occurring with or after lung metastasis. Long-term survival is possible in some patients.

Liposarcoma of the anterior mediastinum and thymus. A clinicopathologic study of 28 cases.

We studied 28 cases of anterior mediastinal liposarcoma occurring in 16 males and 12 females with a mean age of 43 years (range, 14-72). Presenting symptoms included dyspnea (four cases) and chest pain (four cases), although 11 tumors were detected incidentally by routine chest radiography. Seven cases were believed to be located within the thymus. Most (i.e., 25) of the cases were of low grade, with the well-differentiated lipoma-like or sclerosing subtypes constituting 60% and the myxoid subtype constituting 28%; the remaining 12% exhibited mixed features. Three cases were pleomorphic type. Several low-grade tumors exhibited widespread, dense aggregates of mature-appearing lymphocytes and plasma cells, which occasionally obscured the mesenchymal nature of the neoplasm, suggesting instead a lymphoid neoplasm or a reactive fibroinflammatory condition. The three high-grade tumors showed combinations of pleomorphic and round cell patterns, with focal myxoid areas. Of the cases grossly arising within the thymus, only one showed extensive thymic tissue within the lesion ("thymoliposarcoma"); six others exhibited residual thymus peripheral to the tumor. Clinical follow-up in 23 cases revealed recurrence in seven patients (31.8%), with a mean interval to recurrence of 3 years. Eight patients died (mean survival, 2.6 years), one postoperatively and three following a recurrence. Fifteen patients were alive (mean survival, 2 years), four with recurrent tumor. The myxoid tumors had a somewhat more aggressive course than the well-differentiated tumors. Metastases were not observed in any of the patients.

[Anti-HCV antibodies in chronically dialyzed uremic patients. 1-year follow-up study]. / Anticorpi anti-HCV in pazienti uremici cronici dializzati. Studio ad un anno di distanza.

The sera of 109 patients undergoing chronic haemodialysis treatment were reexamined after one year in order to assess changes in the anti-HVC antibody pattern in the intervening period, June 1992-June 1993. Using the ELISA II generation test, positive cases were found to have risen from 57 to 63 (from 52.3% to 57.8%); the Riba II test showed 60 positive cases (previously 52) with 3 undetermined (previously 5). The incidence of biochemical indicators of necrosis and/or cholestasis, negative in HCV patients, also presents a particular positivity (44%) in the presence of four antibody fractions. These data confirm the importance of serial determinations in anti-HCV antibody time, even if they do not correlate directly with the presence of the virus in the circulation and hence with its infecting capacity, the marker for which should be sought in the polymerase chain reaction.

Malignant smooth muscle tumors presenting as mediastinal soft tissue masses. A clinicopathologic study of 10 cases.

BACKGROUND: Smooth muscle tumors presenting as mediastinal soft tissue masses are extremely rare and often are mistaken for other neoplastic conditions. METHODS: Ten cases of patients with malignant smooth muscle tumors presenting as mediastinal soft tissue masses were studied and correlated with their clinical behavior. Tissues were examined histologically and with immunohistochemical stains in all cases, and by electron microscopy in two cases. RESULTS: The patients' ages ranged from 26 to 71 years (mean, 56 years); three were women, and seven were men. Three cases were located in the anterior mediastinum and seven in the posterior mediastinum. The patients with anterosuperior mediastinal tumors all presented with signs and symptoms referable to their lesions; the patients with posterior mediastinal masses (with the exception of one) were all asymptomatic. Grossly, the lesions were well circumscribed and unencapsulated, ranging from 6 to 18 cm in greatest dimension and showed a homogeneous, rubbery cut surface with prominent cystic and myxoid areas. The tumors in all patients appeared to arise from the soft tissues within the mediastinum and were unrelated to adjacent structures. In three patients, the tumors compressed and displaced the esophagus without infiltrating its wall, and in one patient, the tumor was found in close proximity, although unattached, to a large vessel. Histologically, the lesions exhibited a spectrum of morphologic appearances that ranged from low grade leiomyosarcoma with mild-to-moderate nuclear atypia and low mitotic activity (< 3/10 high power fields [HPFs]), to high grade tumors with marked nuclear pleomorphism, extensive areas of necrosis, and high mitotic activity (> 10 mitoses/10 HPFs). One case was characterized by a striking epithelioid morphology with large, round cells arranged in small clusters; another was associated with an incidental microscopic focus of thymic seminoma in the adjacent thymus. Immunohistochemical stains in all cases showed positive labeling of the tumor cells with smooth muscle actin, desmin, and vimentin antibodies. Electron microscopy in two cases showed features of smooth muscle differentiation, i.e., spindle cells surrounded by basal lamina material, immature cell junctions, and abundant intracytoplasmic filaments with focal condensations. All patients were treated with surgical excision. On follow-up, three patients with Stage IIIb and IVa tumors died 2-7 years after surgery, and two patients with Stage Ib and IIb were alive and well 4 and 6 years after surgery, respectively. CONCLUSION: Leiomyosarcomas may arise as primary tumors originating from mediastinal soft tissues in both anterior and posterior compartments. Because of their large size and frequent areas of cystic and myxoid degeneration, they may be confused histologically with neural or other neoplasms. As with their counterparts in other soft tissue locations, histologic grade and clinical stage are the most useful parameters for assessing prognosis.

[Choice of dialysis methods as initial substitutive treatment: trends in the last 10 years]. / Scelta di metodiche dialitiche quale primo trattamento sostitutivo: evoluzione negli ultimi dieci anni.

The authors report data from the Regional Piedmontese Registry about the evolution of choices concerning dialytic therapy in the 20 regional dialysis Units during the years 1981-1990. They confirm a scale-down of acetate dialysis that is replaced with bicarbonate dialysis; besides a limited use of convective dialysis whereas peritoneal dialysis is steady. At the same time they remark an increase in admittance to dialysis and older patients.