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Pseudomyogenic hemangioendothelioma (PMH) is a well-recognized neoplasm that usually arises in the soft tissue; concurrent bone involvement occurs in 24% of cases. PMH of bone without soft tissue involvement is rare. We describe the clinicopathologic findings of 10 such cases, the largest series reported to date. The study included 9 male and 1 female patient; their ages ranged from 12 to 74 years (mean 36.7 y). All patients had multiple tumors with a distinct regional distribution: 45% restricted to the lower extremity; 25% to the spine and pelvis; and 15% to the upper extremity. On imaging studies the tumors were well circumscribed and lytic. The neoplasms were composed of spindled cells arranged in intersecting fascicles with scattered epithelioid cells; epithelioid cells predominated in 3 cases. The neoplastic cells contained abundant densely eosinophilic cytoplasm and vesicular nuclei. There was limited cytologic atypia and necrosis, few mitoses (0 to 2/10 high-power fields), and inconspicuous stroma. Unique findings included abundant intratumoral reactive woven bone and hemorrhage with numerous osteoclast-like giant cells. Immunohistochemically, most tumors were positive for keratin, ERG, and CD31; CD34 was negative. The balanced t(7:19)(q22;13) translocation was documented in 3 cases. Follow-up is limited, but no patient developed documented visceral dissemination, and all have stable or progressive osseous disease. PMH exclusively involving bone is rare. It is multicentric, often involves the lower extremity, and has unusual morphology. The differential diagnosis includes epithelioid vascular neoplasms, giant cell tumor, bone forming neoplasms, and metastatic carcinoma. Because of its rarity, unusual presentation, and morphology, accurate diagnosis can be challenging.

Aims To assess the clinical and histopathological spectrum of primary intra-articular sarcomas. Methods and results Fifteen patients were identified as having primary intra-articular sarcomas and the clinical and pathological features were evaluated. There were nine males and six females who ranged in age from 16 to 84 (mean 44) years. All tumours originated in the knee joint. The pathological diagnoses included: five synovial sarcoma, three extraskeletal myxoid chondrosarcomas, two high-grade myxofibrosarcoma (one conventional, one epithelioid), two undifferentiated pleomorphic sarcoma (one with giant cells) and one each myxoinflammatory fibroblastic sarcoma, conventional hyaline chondrosarcoma, and high-grade myofibroblastic sarcoma. All tumours were treated by segmental resection or amputation. Adjuvant therapy was given in selected cases. Follow-up ranged from 11 to 150 months. Of patients with follow-up, two died of disease; one developed pulmonary metastases after 6 years and was then lost to follow-up. Nine patients were alive and free of disease 12-150 months after diagnosis. Conclusions Primary sarcomas of the joints are very rare and most frequently affect the knee. Our experience indicates that synovial sarcoma and extraskeletal myxoid chondrosarcoma are the most common intra-articular sarcomas.

Primary, adult-type bone fibrosarcoma is an uncommon, malignant spindle-cell tumor of fibroblastic origin, rarely affecting children. Most frequently diagnosed among bone malignancies in the past, improved diagnostic techniques and further restrictive classification criteria have currently made the diagnosis of fibrosarcoma very unusual. We hereby report the case of a 7-year-old child with a right frontal swelling mass. A computed tomography scan showed an osteolytic lesion of the right frontal bone, involving the diploe and the outer table of the skull. An en bloc surgical excision, followed by a thorough immunohistological evaluation, led to the diagnosis of fibroblastic proliferation, with low cellularity and minimal atypias. The patient had four recurrences during the 4-year follow-up. With an increasing histological grade at recurrences, a diagnosis of adult-type fibrosarcoma was made. To the best of the authors’ knowledge, this is the first reported case of an adult-type fibrosarcoma arising in the frontal bone of a child.

Providing the best treatment options and appropriate prognostic information to patients with cartilaginous neoplasms of long bones depends on distinguishing benign from malignant lesions. Correlative interpretation of imaging, histopathology, and clinical information is the current method for making this distinction, yet the reliability of this approach has not been critically evaluated. This study quantifies the interobserver reliability of the determination of grade for cartilaginous neoplasms among a group of experienced musculoskeletal pathologists and radiologists.Nine recognized musculoskeletal pathologists and eight recognized musculoskeletal radiologists reviewed forty-six consecutive cases of cartilaginous lesions in long bones that underwent open biopsy or intralesional curettage. All diagnosticians had a bulleted history and preoperative conventional radiographs for review. Pathologists reviewed the original hematoxylin and eosin-stained glass slides from each case. Radiologists reviewed any additional imaging that was available, variably including serial radiographs, magnetic resonance imaging, and computed tomography scans. Each diagnostician classified a lesion as benign, low-grade malignant, or high-grade malignant. Kappa coefficients were calculated as a measure of reliability.Kappa coefficients for interrater reliability were 0.443 for the pathologists and 0.345 for the radiologists (p0.0001 for both). Kappa coefficients for a subgroup of cases determined to be high risk by subsequent clinical course were poorer at 0.236 and 0.206, respectively (p0.0001 for both). Slightly improved agreement among radiologists was noted for the twenty lesions that had magnetic resonance imaging available (Kappa = 0.437, p0.0001), but not for the lesions analyzed with serial plain radiographs or computed tomography scans.This study demonstrates low reliability for the grading of cartilaginous lesions in long bones, even among specialized and experienced pathologists and radiologists. This included low reliability both in differentiating benign from malignant lesions and in differentiating high-grade from low-grade malignant lesions, both of which are critical to the safe treatment of these neoplasms. This may explain in part the wide variation in outcomes reported for chondrosarcomas treated in different medical centers. New diagnostic and grading strategies linked to protocol-driven treatments are needed, but they must be measured against the long-term gold standard of patient outcomes.

From the Department of Medicine, Division of Gastroenterology and Nutrition, Children’s Hospital (C.P.D.); the Departments of Radiology (S.J.W.) and Pathology (A.E.R.), Massachusetts General Hospital; and the Departments of Pediatrics (C.P.D.), Radiology (S.J.W.), and Pathology (A.E.R.), Harvard Medical School — all in Boston.

Progressive extraskeletal ossification is the defining feature of a group of very rare genetic syndromes, including fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. Recent advances in human molecular genetics have enabled the molecular characterization of disease-causing mutations for some of these conditions1,2. Despite our increasing understanding of the biochemical etiology of heterotopic ossification syndromes and newly applicable molecular genetic screening tools, individual patients with progressive heterotopic ossification still pose a difficult diagnostic challenge. We report the case of a female patient with a four-decade history of recurrent, progressive heterotopic ossification limited to the right hemicorporeum. This condition, which does not meet the clinical or molecular diagnostic criteria of any known syndrome, represents a new syndrome of heterotopic ossification, which we have named focal fibronodular heterotopic ossification. Our patient was informed that data concerning the case would be submitted for publication. A sixty-three-year-old right-hand-dominant woman presented to our institution for evaluation and treatment of a complex deformity of the right upper extremity. Distinctive features of the deformity at the time of presentation included multiple firm nodular soft-tissue masses located on the dorsal and volar surfaces of the right hand and wrist, involving the thumb, index finger, and long fingers. The patient had severe contractures of the index finger and first web space in areas of particularly large and dense nodule formation; small skin ulcerations that appeared to be chronic and infected were seen in these areas and at the volar base of the first metacarpal (Figs. 1-A, 1-B, and 2). The patient had a concomitant dense sensory and motor neuropathy of the median nerve of the right hand. Full physical examination revealed other areas of hard, nodular swelling, specifically in the patient's right shoulder, right upper arm, right lateral forefoot, and right iliac crest. Notably, the …

Aim: Post-streptococcal glomerulonephritis (PSGN) is a frequent cause of acute nephritis in children. Numerous studies have described PSGN in high-risk populations yet few data describing PSGN in a low-incidence population exist. This study aimed to describe the epidemiology, clinical manifestations, diagnosis, complications and outcomes of PSGN in an urban Australian population. Methods: A 16-year retrospective review of case notes and laboratory data was conducted at a tertiary Sydney paediatric hospital. Results: Thirty-seven children were treated for PSGN with a mean age of 8.1 years (range 2.6–14.1 years). Twenty-eight subjects (75.7%) had a history of a recent upper respiratory tract or skin infection. Hypertension and/or oedema was present in 29 subjects (78.4%). Streptococcal pharyngitis was identified as the likely source in 17 subjects (45.9%). Skin infections occurred less frequently. Antibodies against streptolysin O, streptokinase or deoxyribonuclease B were elevated when a single titre was measured in 35 subjects (94.6%). Thirty subjects (81.1%) developed renal impairment (median peak creatinine, 95 µmol/L, range 39–880 µmol/L). No correlation was demonstrated between peak creatinine, age, ethnicity, streptococcal titres and serum complement levels. The mean length of admission was 8.2 days. Seven subjects (18.9%) had a complicated course with three subjects requiring dialysis. Only one subject has ongoing renal dysfunction. Conclusion: Significant differences are seen in a low-incidence urban Australian population with PSGN when compared with endemic or epidemic disease in high-risk populations. The higher rates of complications that were seen compared with previously studied populations need further clarification.

Primary synovial chondromatosis is a proliferation of cartilaginous bodies within the synovial membrane, bursa, or tendon sheath. Historically, it has been characterized as a rare, monoarticular, benign arthropathy of uncertain etiology, typically involving a single large joint in a young adult. Males are affected more commonly than females1. The knee is involved most frequently, followed by the hip, elbow, shoulder, ankle, and wrist2-4; however, smaller joint involvement, including that of the spine, foot, and hand, has been reported5-8, as has involvement of the acromioclavicular, temporomandibular, and sternoclavicular joints9-12. The Massachusetts General Hospital tumor database contains eighty-six recorded cases of synovial chondromatosis; these cases include involvement of the knee (thirty-three cases), the hip (sixteen cases), the shoulder (eight cases), the ankle (seven cases), the foot (seven cases), the elbow (five cases), and miscellaneous locations (ten cases). Malignant degeneration of synovial chondromatosis into chondrosarcoma is a described, but extremely rare, event. We describe a unique case of synovial chondromatosis in the shoulder, which, following multiple recurrences with a repeatedly benign histologic appearance but abnormal results on deoxyribonucleic acid (DNA) flow cytometry, ultimately demonstrated histologic evidence of malignant transformation. The aneuploid DNA of this specimen distinguishes it from all other cases of synovial chondromatosis in the Massachusetts General Hospital tumor database. Our patient was informed that data concerning the case would be submitted for publication. A forty-seven-year-old man presented in February of 1999 with a two-year history of right shoulder pain and generalized shoulder discomfort that was most frequently related to activity. In addition, the patient reported that lying on the shoulder at night caused pain. The patient had not experienced trauma or any other inciting event, nor did he have any motor or sensory deficits or any additional …

Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM.A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors.At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p0.01), radiation dose64 Gy (p0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p = 0.05). Patients receiving64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% ifor =64 Gy, p0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p0.001. Other known prognostic factors, including grade, stage, size, and age (50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p0.01 and dose (64 vs.or =64 Gy), p0.05; the best predictors for OS were size, p0.001, gross vs. microscopic PM, p0.05, and LF, p0.01.Local control is achieved in most PM STS patients undergoing RT. Doses64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions5 cm, grossly positive margins, and after local failure.

Angiosarcomas are an uncommon type of malignancy that are generally thought to behave usually in a locally aggressive fashion; they often metastasize to distant sites. Patients with a diagnosis of angiosarcoma treated at our institution between 1980 and 2006 were analyzed for patient demographics, tumor characteristics, multimodality treatment, and outcomes. A total of 82 patients were divided into those with primary and advanced disease. Overall, the median age was 65 (range, 22–91) years, and 44% of patients were women. Median size of tumors was 3.8 cm, and 76% of tumors were intermediate or high grade. Tumors were located throughout the body: 32 cutaneous, 22 deep soft tissues or organs, 10 radiation or lymphedema field, 8 bone, and 7 nonirradiated breast. Of 46 patients with primary disease, all patients underwent surgical resection, 67% received radiotherapy, and 27% received chemotherapy. Five-year disease-specific survival was 60%, and negative prognostic factors included intermediate or high grade, and tumors arising in a radiated or lymphedema field. Of 36 patients with advanced disease, 36% underwent a palliative operation, 78% received radiation, and 58% received chemotherapy. Median survival was just 7.3 months, and cutaneous tumors predicted a better prognosis compared with other sites. Primary angiosarcomas treated with aggressive surgical resection and the addition of radiation for close margins or worrisome pathologic features can result in long-term survival in most patients. The role of adjuvant chemotherapy is unclear. Patients with advanced disease have a poor prognosis, but there can be dramatic responses to chemotherapy in a minority of patients.

Imaging criteria for measuring the response of desmoid fibromatosis to systemic therapy are not well established. We evaluated a series of patients with desmoids who underwent systemic therapy to document magnetic resonance imaging (MRI) features associated with a positive clinical response. This Institutional Review Board-approved retrospective study included 23 patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were categorized as progressive disease, stable, or partial response. Maximum tumor dimension (Dmax), approximate tumor volume (VTumor), and quantitative tumor T2 hyperintensity and contrast enhancement (relative to muscle) for pre- and post-treatment MRIs were compared. Three lesions progressed, 5 lesions were stable, whereas 21 showed a clinical response. Dmax decreased more in responders (mean −11.0 %) than in stable/progressive lesions (mean −3.6 and 0 % respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 27 out of 29 lesions were “stable,” including the 3 progressive lesions. In responders, VTumor change averaged −29.4 %, but −19.2 % and +32.5 % in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria 14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50–54 % in partial response/stable disease, but only by 10 % in progressive lesions (p = 0.049, t test). Changes in contrast enhancement ranged from −23 % to 0 %, but were not statistically significant among response groups (p = 0.37). Change in T2 hyperintensity showed a positive correlation with volumetric change (r = 0.40). Decreases in volume and T2 hyperintensity reflect the positive response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not sensitive to clinically determined tumor response.

Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels of receptor activator of nuclear factor κ-B ligand (RANKL). Denosumab, a RANKL inhibitor, which is clinically used to treat GCT, leads to a marked alteration in the histologic appearance of the tumor with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other primary tumors of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant transformation. To histologically characterize tGCT, we identified 9 cases of GCT biopsied or resected after denosumab treatment. tGCT cases included 16 specimens from 9 patients including 6 female and 3 male individuals aged 16 to 47 (median 32) years. Duration of treatment varied from 2 to 55 months. We compared these tumors with malignant neoplasms arising in GCTs (n=9). The histology of tGCT was variable but appeared to relate to the length of therapy. All tGCTs showed marked giant cell depletion. Early lesions were highly cellular, and the combination of cellularity, atypia, and haphazard bone deposition caused the lesion to resemble high-grade osteosarcoma. Unlike de novo high-grade osteosarcoma or malignancies arising in GCT, however, tGCT showed less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. Tumor in patients on prolonged therapy showed decreased cellularity and abundant new bone, deposited as broad, rounded cords or long, curvilinear arrays. The latter morphology was reminiscent of low-grade central osteosarcoma, but, unlike low-grade central osteosarcoma, tGCT was negative for MDM2 and again lacked an infiltrative growth pattern. Overall, tGCT may have a wide range of morphologic appearances. Because the treated tumors bear little resemblance to their pretreatment counterparts, careful attention to the history of denosumab administration is crucial to avoid a misdiagnosis with an important impact on therapy. Unlike malignant GCTs, tGCTs lack significant nuclear atypia, mitotic activity, and infiltration of preexisting bone, but instead show a unique pattern of intralesional bone deposition.

OBJECT Spinal chordomas can have high local recurrence rates after surgery with or without conventional dose radiation therapy (RT). Treatment outcomes and prognostic factors after high-dose proton-based RT with or without surgery were assessed. METHODS The authors conducted a retrospective review of 126 treated patients (127 lesions) categorized according to disease status (primary vs recurrent), resection (en bloc vs intralesional), margin status, and RT timing. RESULTS Seventy-one sacrococcygeal, 40 lumbar, and 16 thoracic chordomas were analyzed. Mean RT dose was 72.4 GyRBE (relative biological effectiveness). With median follow-up of 41 months, the 5-year overall survival (OS), local control (LC), locoregional control (LRC), and distant control (DC) for the entire cohort were 81%, 62%, 60%, and 77%, respectively. LC for primary chordoma was 68% versus 49% for recurrent lesions (p = 0.058). LC if treated with a component of preoperative RT was 72% versus 54% without this treatment (p = 0.113). Among primary tumors, LC and LRC were higher with preoperative RT, 85% (p = 0.019) and 79% (0.034), respectively, versus 56% and 56% if no preoperative RT was provided. Overall LC was significantly improved with en bloc versus intralesional resection (72% vs 55%, p = 0.016), as was LRC (70% vs 53%, p = 0.035). A trend was noted toward improved LC and LRC for R0/R1 margins and the absence of intralesional procedures. CONCLUSIONS High-dose proton-based RT in the management of spinal chordomas can be effective treatment. In patients undergoing surgery, those with primary chordomas undergoing preoperative RT, en bloc resection, and postoperative RT boost have the highest rate of local tumor control; among 28 patients with primary chordomas who underwent preoperative RT and en bloc resection, no local recurrences were seen. Intralesional and incomplete resections are associated with higher local failure rates and are to be avoided.

Perioperative thrombotic complications after orthopedic surgery are associated with significant morbidity and mortality. The use of aspirin to reduce perioperative cardiovascular complications in certain high-risk cohorts remains controversial. Few studies have addressed aspirin use, bleeding, and cardiovascular outcomes among high-risk patients undergoing joint and spine surgery.We performed a retrospective comparison of adults undergoing knee, hip, or spine surgery at a tertiary care center during 2 periods between November 2008 and December 2009 (reference period) and between April 2013 and December 2013 (contemporary period).Patient demographics, comorbidities, management, and outcomes were ascertained using hospital datasets.A total of 5690 participants underwent 3075 joint and spine surgeries in the reference period and 2791 surgeries in the contemporary period. Mean age was 61±13 years, and 59% were female. In the overall population, incidence of myocardial injury (3.1% vs 5.8%, P.0001), hemorrhage (0.2% vs 0.8%, P=.0009), and red blood cell transfusion (17.2% vs 24.8%, P.001) were lower in the contemporary period. Among 614 participants with a preoperative diagnosis of coronary artery disease (CAD), in-hospital aspirin use was significantly higher in the contemporary period (66% vs 30.7%, P.0001); numerically, fewer participants developed myocardial injury (13.5% vs 19.3%, P=.05), had hemorrhage (0.3% vs 2.1%, P=.0009), and had red blood cell transfusion (37.2% vs 44.2%, P.001) in the contemporary vs reference period.In a large tertiary care center, the incidence of perioperative bleeding and cardiovascular events decreased over time. In participants with CAD, perioperative aspirin use increased and appears to be safe.

Purpose of review This article reviews the current literature on tumor-infiltrating immune cells in gastrointestinal stromal tumor (GIST), and the current status and prospects of effective immunotherapeutic strategies. Recent findings Tumor-infiltrating immune cells populate the microenvironment of GISTs; the most numerous are tumor-associated macrophages (TAMs) and CD3 T cells. TAMs have not been shown to have a relationship with the biological behavior of GISTs; however, the number of CD3 T cells correlates with better outcomes. The prognostic significance of tumor-infiltrating neutrophils, natural killer cells, CD4 T cells, CD8 T cells, and Treg cells remains unknown.Imatinib mesylate achieves a clinical response in 80% of patients with GIST. Its antitumor mechanism is partially immune mediated. The combination of imatinib and interferon-α has been shown to be effective against GIST - it eradicates tumor cells including those that are drug resistant. Preclinical trials including cytotoxic T lymphocyte-associated antigen 4 blockade, anti-KIT antibody, and the generation of designer T cells have shown promising therapeutic effect in animal models of GIST. Summary GIST contains many tumor-infiltrating immune cells and should be susceptible to immunotherapy; early clinical and preclinical trials have shown promising results that should lead to new investigations and effective forms of direct and synergistic therapies.

Alumina-on-alumina articulations were first introduced into total hip arthroplasty in 1970 by Boutin et al. in France [3], and were approved by the Food and Drug Administration for their use in the USA in 1982. The ceramic-on-ceramic coupling was intended to reduce wear and particulate debris generated by metal-on-plastic articulations being used at that time. Modern alumina-on-alumina articular couplings have extremely low wear rates [1, 6, 10, 12, 15, 18] on the order of 0.004 mm3 per million cycles [2, 11, 17]. Early concerns for ceramic fractures have been addressed by improvements in the alumina material [11, 15, 19] and, in some cases, the introduction of a metal backing to the alumina acetabular insert [4, 8]. Modern fracture rates are estimated at 0.04% for ceramic femoral heads and 0.015% for ceramic acetabular liners [7, 8, 14]. Three cases of metal-backed acetabular liner fracture requiring reoperation were reported over the past 5 years, all occurring more than 2 years after the original surgery [4, 5]. We report a case of acetabular rim fracture and extreme wear due to the vertical positioning of the acetabular component of an alumina-on-alumina total hip coupling with a metal-backed acetabular insert and its associated benign particle-induced soft tissue reaction.

Lipomatous metaplasia is an uncommon phenomenon. After identifying the presence of a band of adipocytes in the superficial reticular dermis underlying two excisions for basal cell carcinoma, we prospectively reviewed all skin specimens accessioned in our laboratory over a 6-month period and identified eight additional cases. In each example there was a band of adipocytes in the upper dermis, at the level of solar elastosis that was widely separated from the subcutaneous fat by a normal appearing reticular dermis. The cells were positive for S100 and negative for CD163. No connection between the superficial band of adipocytes and the subcutaneous or periappendageal fat was seen. The alterations were flat in configuration without polypoid changes. Eyerich et al. reported lipomatous metaplasia in the dermis of a patient with acute generalized exanthematic pustulosis and psoriasis, and postulated this to be a postinflammatory phenomenon. Fatty metaplasia occurs within a variety of cutaneous neoplasms including nevi, adnexal tumors and peripheral nerve sheath tumors. However, superficial dermal fatty metaplasia beneath cutaneous neoplasms is a newly described phenomenon and we suspect this process represents fatty metaplasia within solar elastosis and that it may occur more frequently than recognized.

In this paper, we report the results of dimercaptosuccinic acid studies performed in infants under 1 year of age at risk of renal scarring

Background A 17-year-old male presented with pain in his lower-left chest. He had no significant medical history and was previously in good health. He had a fractured ninth left anterior rib and the tenth, eleventh and twelfth ribs were absent, which was thought to be a congenital anomaly. Several months later, he presented again with back pain, an enlarging mass in the lower-left chest wall, erosion of the lateral pedicles of the lower thoracic vertebrae and pleural effusion. Investigations Physical examination, chest X-ray, MRI of the spine, incisional biopsy, serial CT imaging of the hemithorax, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assays. Diagnosis Gorham's lymphangiomatosis with expression of platelet-derived growth factor receptor-β and elevated circulating platelet-derived growth factor-BB. Management Spine stabilization, thalidomide, celecoxib, interferon-α2b, pamidronate, zoledronate, thoracotomy, pleurectomy, talc pleurodesis, and imatinib mesylate.

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received ≥73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by ≥73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option.

Chordomas in children and adolescents comprise

It has recently been suggested that peripheral nerve or plexus blocks performed with the use of a nerve stimulator at low currents (

Purpose Unilateral mandibular distraction osteogenesis (DO) has been shown to cause gross changes in the mandibular condyle and articular disc. The purpose of this study was to correlate histologic findings with these gross changes in a minipig distraction model. Materials and Methods Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0-day latency and rates of 1, 2, or 4 mm/day for a 12-mm gap. After the minipigs were killed (at 0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested, decalcified, prepared for standard paraffin embedding, and evaluated to determine changes in 1 ) morphology and thickness of the articular cartilage and subchondral bone and 2 ) morphology of the disc. Results In control animals, there were no degenerative changes in the articular cartilage and underlying condylar bone; there were no significant differences in the mean articular cartilage thickness. The temporomandibular joint discs were normal. In experimental animals, distracted condyles showed increasing degenerative changes and mean articular cartilage thickness as the DO rate increased. The discs were thinner. These changes were present, but to a lesser degree, in the contralateral condyles. After 90 days, degenerative changes in the condyles and discs were reduced, after remodeling, except in the 4 mm/day DO group. Conclusions Histologic changes in the condyles and temporomandibular joint discs in response to mandibular DO correlated with previously reported gross changes. These changes were greater at higher distraction rates and remodeling back to normal occurred in mandibular condyles distracted at 1 mm/day.

Increased attention has been directed at the quality of randomized controlled trials (RCTs) and how they are being reported. We examined leading anesthesiology journals to identify if there were specific areas for improvement in the design and analysis of published clinical studies. All RCTs that appeared between January 2000 and December 2000 in leading anesthesiology journals (Anesthesiology,Anesthesia & Analgesia,Anaesthesia, and Canadian Journal of Anaesthesia) were retrieved by a MEDLINE search. We used a previously validated assessment tool, including 14 items associated with study quality, to determine a quality score for each article. The overall mean weighted quality score was 44% +/- 16%. Overall average scores were relatively high for appropriate controls (77% +/- 7%) and discussions of side effects (67% +/- 6%). Scores were very low for randomization blinding (5% +/- 2%), blinding observers to results (1% +/- 1%), and post-beta estimates (16% +/- 13%). Important pretreatment clinical predictors were absent in 32% of all studies. Significant improvement in the reporting and conduct of RCTs is required and should focus on randomization methodology, the blinding of investigators, and sample size estimates. Repeat assessments of the literature may improve the adoption of guidelines for the improvement of the quality of randomized controlled trials.

Multiple gastrointestinal stromal tumors typically occur in familial form associated with KIT receptor tyrosine kinase or platelet-derived growth factor receptor-alpha (PDGFRA) germline mutations, but may also develop in the setting of type 1 neurofibromatosis. The molecular abnormalities of gastrointestinal stromal tumors arising in neurofibromatosis have not been extensively studied. We identified three patients with type 1 neuro-fibromatosis and multiple small intestinal stromal tumors. Immunostains for CD117, CD34, desmin, actins, S-100 protein, and keratins were performed on all of the tumors. DNA was extracted from representative paraffin blocks from separate tumor nodules in each case and subjected to a nested polymerase chain reaction, using primers for KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18, followed by direct sequencing. The mean patient age was 56 years (range: 37-86 years, male/female ratio: 2/1). One patient had three tumors, one had five, and one had greater than 10 tumor nodules, all of which demonstrated histologic features characteristic of gastrointestinal stromal tumors and stained strongly for CD117 and CD34. One patient died of disease at 35 months, one was disease free at 12 months and one was lost to follow-up. DNA extracts from 10 gastrointestinal stromal tumors (three from each of two patients and four from one patient) were subjected to polymerase chain reactions and assessed for mutations. All of the tumors were wild type for KIT exons 9, 13, and 17 and PDGFRA exons 12 and 18. Three tumors from one patient had identical point mutations in KIT exon 11, whereas the other tumors were wild type at this locus. We conclude that, although most patients with type 1 neurofibromatosis and gastrointestinal stromal tumors do not have KIT or PDGFRA mutations, KIT germline mutations might be implicated in the pathogenesis of gastrointestinal stromal tumors in some patients.

Bone marrow transplant nephropathy (BMTN) classically presents more than 100 days after transplantation as an acute nephritis with hypertension, azotaemia and anemia that usually results in end stage renal failure (ESRF). The risk of developing BMTN may be greater with the use of more intensive chemotherapy and higher total body and tumor bed irradiation. Cis-retinoic acid (RA) may further increase the risk of developing BMTN. Here, we report the cases of two children who developed typical clinical and biochemical features of BMTN. They were both treated for stage IV neuroblastoma with chemotherapy, bone marrow transplant (BMT) conditioning that included total body irradiation and RA therapy after BMT, although the patient in case 1 had established renal insufficiency prior to the commencement of RA. Renal biopsy of these children showed classical BMTN histology, and the renal manifestations progressed quickly; the patient in case 1 became dialysis dependent by 1 year post-bone marrow transplant. Recently, RA has been added to the post-BMT therapy in children with stage IV neuroblastoma. The occurrence of BMTN in two children treated with RA in our unit is unlikely to be coincidental. Although RA has been shown to confer a significant survival advantage in this disease, animal studies and a previous case report have suggested it could increase the toxic effects of chemotherapy and renal irradiation. It is likely that RA contributed to the deterioration in renal function in these patients.

During the past 30 years, the orthopaedic oncology group at the Massachusetts General Hospital has treated 648 patients with osteosarcoma centrally located in the bone. Using records maintained in a specifically designed computer system, a study was done to assess the factors that seemed to influence the survival outcome. The overall survival for the entire series was 68% at an average followup of 6 +/- 4 years. Death occurred at a mean of 3 +/- 3 years. Patient gender had no effect, but age of the patient was correlated with survival data, with the poorest survival for the older patients. Surgical treatment had no effect on outcome, but the Musculoskeletal Tumor Society stage of the lesion, the presence of metastases or local recurrence, and the chemotherapeutic treatment (very dependent on the drugs available and adjuvant versus neoadjuvant administration at various decades) all had a profound effect. In addition, anatomic location, size of the tumor, and percentage of tumor cells killed after neoadjuvant chemotherapy all had an effect on outcome.

BK virus (BKV) is recognized as a significant cause of renal allograft dysfunction in adults, and there is growing awareness of its importance in the pediatric population. Eighteen pediatric renal transplant recipients and 18 age-matched controls were prospectively studied. Anti-BKV immunoglobulin G (IgG) and IgM titres were assayed in all subjects at entry to the study. Polymerase chain reaction (PCR) for BKV DNA was performed on urine and serum at entry, and prospectively tested again at 4, 8 and 12 months. Mean age +/- s.d. of transplant recipients and controls was 14.6 +/- 3.3 and 13.9 +/- 0.33 yr respectively [not significant (NS)]. Transplant patients were studied at a mean time of 5.6 +/- 4.2 yr post-transplant. 56% of transplant patients and 39% of controls were seropositive (+ve BKV IgG) (NS). Plasma BKV PCR was positive in one transplant patient (who also had positive urine PCR) and in none of the controls. The prevalence of positive urine PCR in transplant patients was greater than in controls (33% vs. 0%, p = 0.02). Positive urine BKV PCR was more commonly found in patients treated with mycophenolate than azathioprine (p = 0.04). We conclude that the prevalence of BKV seropositivity and viral activation in this Australian pediatric renal transplant population is similar to that reported in adult and pediatric populations in other countries. BK viruria was more common in children with greater immunosuppression, suggesting that this group is at higher risk of BKV induced nephropathy.

External anatomic landmarks have traditionally been used to approximate the location of the neck blood vessels to optimize central venous cannulation of the internal jugular vein (IJV) while avoiding the common carotid artery (CCA). Head rotation affects vessel orientation, but most landmark techniques do not specify its optimal degree. We simulated catheter insertion via both an anterior and central approach to the right IJV using an ultrasound probe held in the manner of a syringe and needle in 49 volunteers. Increased head rotation from 0 degrees, 15 degrees, 30 degrees, 45 degrees, and 60 degrees to the left of midline was associated with higher probability of a simulated needle contacting the IJV and the CCA. For both approaches, the risk of CCA contact was10% for head rotations ofor=45 degrees. Increased body surface area (BSA) and body mass index (BMI) were associated with more CCA contact at head rotations of 45 degrees or 60 degrees. To optimize IJV contact while reducing the likelihood of inadvertent contact with the CCA, the head should be rotated no more than 30 degrees in patients with high BMI or BSA, but it may be turned to 60 degrees if BMI or BSA is low.

The viral disease, smallpox, was well known through the end of the 20th Century. Because it has been eradicated from natural populations, the present clinical experience with managing the disease is limited. Similarly, research in the pathophysiology, treatment, and prevention of the disease has recently become a priority. Concerns regarding smallpox as a weapon of bioterrorism have led to the implementation of a new prophylactic vaccine program, a renewal in variola vaccine research, and treatment regimens against variola infection.

Aneurysmal bone cyst (ABC) is a locally aggressive osseous lesion that typically occurs during the first two decades of life. ABC was regarded historically as a nonneoplastic process, but recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs. Herein we show that a recurring ABC chromosomal translocation t(16;17)(q22;p13) creates a fusion gene in which the osteoblast cadherin 11 gene (CDH11) promoter region on 16q22 is juxtaposed to the entire ubiquitin-specific protease USP6 (Tre2) coding sequence on 17p13. CDH11-USP6 fusion transcripts were demonstrated only in ABC with t(16;17) but other ABCs had CDH11 or USP6 rearrangements resulting from alternate cytogenetic mechanisms. CDH11 is expressed strongly in bone, and our findings implicate a novel oncogenic mechanism in which deregulated USP6 transcription results from juxtaposition to the highly active CDH11 promoter.

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.

Summary: Although relatively common, soft tissue tumors frequently present diagnostic problems for practicing pathologists. Immunohistochemistry has facilitated the diagnosis of many mesenchymal tumors; however, there is considerable overlap in the staining profiles among cells demonstrating fibroblastic and myofibroblastic differentiation. It has been our experience that soft tissue tumors associated with abundant extracellular collagen deposition commonly cause problems in classification. One reason for this is that tumors displaying this morphology include representatives from different histogenetic families. Specifically, tumors exhibiting fibroblastic, myofibroblastic and even lipomatous differentiation may manifest as a densely collagenous mass. It is the purpose of this review to highlight these collagen-rich soft tissue tumors.

Presentation of Case A nine-year-old girl was admitted to the hospital because of hepatosplenomegaly and pain in the thigh. The patient had been well until three years earlier, when she began to have frequent episodes of epistaxis. Two years before admission, mild abdominal distention developed. Periodic examinations by her physician were reported to have revealed no abnormalities. Two months before admission, the abdominal distention worsened but was not accompanied by abdominal pain. Physical examination revealed hepatosplenomegaly. An abdominal ultrasonographic study confirmed the presence of hepatosplenomegaly, without evidence of portal-vein thrombosis (Figure 1). The results of liver-function tests were normal or . . .

Although the majority of mesenchymal lesions of the gastrointestinal tract are neoplastic in nature, nonneoplastic reactive processes may involve the gastrointestinal tract and mesentery, causing diagnostic confusion with more aggressive neoplasms, such as fibromatosis or gastrointestinal stromal tumors. In this study, we report a series of fibroinflammatory lesions of the gastrointestinal tract that we think represent a relatively cohesive group of tumors and describe the clinical and pathologic features of this entity, which we have termed "reactive nodular fibrous pseudotumor." The tumors affected five patients (four male and one female patient) who ranged in age from 48 to 71 years (mean 56 years). Two patients presented with acute abdominal pain without a significant past medical history, two had incidental lesions discovered during evaluation for other medical conditions, and one was found to have an abdominal mass. Three patients had a history of abdominal surgery. The tumors were multiple in three patients and solitary in two patients. In four cases, at least one of the tumors involved the small intestine or colon, and the lesion was confined to the peripancreatic soft tissue in one case. The tumors were firm, tan-white, ranged in size from 4.3 to 6.5 cm in greatest dimension, and were grossly well circumscribed. All of the lesions were of low to moderate cellularity and composed of stellate or spindled fibroblasts arranged haphazardly or in intersecting fascicles. Three cases had microscopically infiltrative borders. The stroma was rich in collagen, which was wire-like, keloidal, or hyalinized. Intralesional mononuclear cells were sparse but were more numerous peripherally and frequently arranged in lymphoid aggregates. Immunohistochemical stains demonstrated that all of the tumors stained for vimentin, 80% stained for CD117 or muscle specific actin, 60% stained for smooth muscle actin or desmin, and none of the tumors stained for CD34, S-100 protein, or anaplastic lymphoma kinase-1. Follow-up information was available in all cases: four patients had no residual disease following surgical resection (mean follow-up 16.3 months) and one patient who had an incomplete surgical resection had stable disease at 26 months. In summary, we report a series of distinct intraabdominal fibroinflammatory pseudotumors that we have collectively termed "reactive nodular fibrous pseudotumors." These lesions are uncommon and may infiltrate the bowel wall, thereby mimicking primary bowel neoplasms or intraabdominal fibromatosis. Recognition of these nonneoplastic lesions is important, as they pursue a benign clinical course, but may be confused with other mesenchymal neoplasms that require more aggressive treatment.

The objective of this prospective study was to determine the prevalence of hyperlipidemia in our pediatric renal transplant patients and to treat those with persistently elevated cholesterol and/or low-density lipoprotein (LDL) levels. All patients with a functioning renal allograft for greater than 6 months were studied (n = 18). Patients with cholesterol and/or LDL levels greater than the 95th percentile (n = 9) were commenced on an HMG-CoA reductase inhibitor, Atorvastatin and monitoring was performed for efficacy and adverse effects. Total serum cholesterol was elevated in 11 of 18 (61%) and triglyceride (TG) was elevated in 12 of 18 (67%) patients. Atorvastatin treatment was effective with a mean percentage reduction of total cholesterol of 41 +/- 10% (p < 0.01 vs. before treatment), LDL 57 +/- 7% (p < 0.01 vs. before treatment) and TG 44 +/-25% (p = 0.05 vs. before treatment). No adverse effects on allograft function or cyclosporin levels were experienced. Hyperlipidemia is a common problem and Atorvastatin is a safe and effective treatment in pediatric renal transplant recipients.

Purpose: Distraction osteogenesis (DO) is a commonly used technique for mandibular lengthening, but changes in the temporomandibular joint have not been well documented. The purpose of this study was to evaluate the effect of DO, at varying rates, on the mandibular condyle and articular disc. Materials and Methods: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0 day latency and rates of 1, 2, or 4 mm/d for a 12-mm gap. After the animals were killed (0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested and evaluated to determine changes in 1) condylar form and size, 2) condylar surface, and 3) the articular disc. Results: Articular surfaces of the condyles in control animals were smooth, with no irregularities or erosions. In animals undergoing distraction, ipsilateral condyles showed increasing changes in morphology and AP dimension, and surface contour irregularities as the DO rate increased. These changes were present, but to a lesser degree, in the contralateral condyles. Articular discs of both ipsilateral and contralateral sides showed variable thinning at the medial aspect at end DO. After 90 days, changes in the condyles and discs were reduced by remodeling except in the 4 mm/d DO groups. Conclusions: Results of this preliminary study indicate that gross changes occur in condyles and discs after unilateral mandibular DO. These changes are more severe at faster distraction rates (4 mm/d) and tend to resolve during neutral fixation when a rate of 1 mm/d is used. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:1327-1333, 2002