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The successful evolution of an effective drug depends on its pharmacokinetics, efficiency and safety and these in turn depend on the drug-target/drug-carrier protein binding. This work, deals with the interaction of a pyridine derivative, 2-hydroxy-5-(4-methoxyphenyl)-6-phenylpyridine 3-carbonitrile (HDN) with serum albumins at physiological conditions utilizing the steady state and time-resolved fluorescence techniques by probing the emission behavior of Trp in BSA and HSA. In-silico studies revealed a combined static and dynamic quenching mechanism for the interactions. The binding studies suggests a spontaneous binding between HDN and the albumins with a moderate binding affinity (Kb ∼ 10 -5  M-1) with a single class of binding site. The FRET mediated emission from HDN indicates preferential binding of HDN in subdomain IIA of the albumins with Trp residue in close proximity. Circular dichroism results indicate HDN induced conformational changes for BSA and HSA, but the α-helical secondary structure was well preserved even up to a concentration of 10 µM HDN. Moderate binding affinity of HDN with BSA and HSA and the unaltered secondary structure of proteins on binding propose the potential application of HDN as an efficient drug. The application of docking method on the affinity of HDN towards the proposed target/receptor is discussed., (Copyright © 2022. Published by Elsevier B.V.)

Multicentric osteosarcoma (M-OGS) is characterized by multicentricity of osseous osteosarcomas, either synchronous or metachronous, without visceral involvement. The study's purpose was to clinicopathologically and radiographically analyze 56 cases of M-OGS (22 synchronous and 34 metachronous). The distal femur was the most common site. Histologically, all tumors were high grade. Of 22 patients with synchronous M-OGS, 16 had 3 or more simultaneous tumors; the axial skeleton was involved in 14 (64%) of 22 cases. In metachronous M-OGS, the second malignancy occurred after a median of 22 months. Treatment was surgery, chemotherapy, radiotherapy, or a combination of these. Patients with metachronous osteosarcoma had a median survival longer than did patients with synchronous tumors. Overall, 8 long-term survivors were treated by aggressive surgery with wide margins (plus chemotherapy and/or radiotherapy). M-OGS combines multiple skeletal locations of high-grade conventional osteosarcomas and has a poor prognosis. Aggressive surgery may result in improved long-term survival, particularly in patients with metachronous disease.

Primary schwannoma of the bone, defined as arising within the medullary cavity and radiologically mimicking more common primary bone tumors, is rare. We present 17 tumors, 13 conventional schwannomas, and 4 melanotic type. Collectively, they represented <1% of all primary bone tumors seen at Mayo Clinic over a 33-year period. Most tumors affected long bones. There was a slight female predilection. Fifteen tumors were sporadic, and 2 were syndrome associated (Carney complex). Pain was the most common symptom. Given their rarity, schwannomas of the bone are not usually included in the differential diagnosis of primary osseous spindle cell tumors. Thus, they are prone to misdiagnosis and overtreatment. Similar to their more common extraosseous counterparts, primary schwannomas of the bone behave in a benign manner and are successfully treated by local excision alone.

Benign bone tumors frequently pose a diagnostic challenge for general surgical pathologists. Accurate pathologic diagnosis requires careful clinical and radiological correlation. The most significant recent advances in some benign bone tumors have occurred at the molecular and cytogenetic level. The detection of clonal chromosomal aberrations, various specific molecular genetic events, and the description of the bone cell signaling pathways in the field of osteoimmunology have provided a better understanding of the pathophysiology of certain tumors and an important aid in the diagnostic workup and differential diagnosis of some bone lesions demonstrating overlapping clinical and pathologic features. Future directions include prognostic and therapeutic applications of these findings. Newer less invasive therapeutic techniques and medical management have been developed for the treatment of certain benign bone tumors.

Purpose: To provide a comprehensive review of metastasizing (malignant) ameloblastoma, establish a new baseline of valid cases using histologic criteria and minimum documentation, and report 3 cases from the Mayo Clinic files., Patients and Methods: Ninety-eight original reports of "metastasizing," "malignant," or "atypical" ameloblastoma were reviewed. The following data were gathered for reports that demonstrated well-differentiated ameloblastoma at the metastatic site: gender, ethnicity, age at time of primary tumor diagnosis, histologic pattern of primary tumor, anatomic sites of primary and metastatic tumors, interval from diagnosis of primary to diagnosis of metastasis, number of recurrences preceding metastasis, treatment responses to radiation and/or chemotherapy, presence of hypercalcemia, and length of survival after metastasis., Results: Twenty-seven valid reports of metastasizing (malignant) ameloblastoma were identified; 81% originated in the mandible, recurring on average 4 times before metastasis. Lungs were the initial site of metastasis in 78% of reports, of which 71% were bilateral. The average time from diagnosis of primary to metastasis was 18 years. Over half of the patients were alive and had survived an average of 10 years since diagnosis of metastasis. Those patients who had succumbed to their disease had an average survival time of 3 years after diagnosis of metastasis., Conclusions: Metastasis of well-differentiated ameloblastoma occurs more rarely than previously believed. Metastasis to the lungs bilaterally, by the hematogenous route, usually follows multiple failed attempts at primary tumor control. The absence of malignant cytologic transformation correlates with relatively indolent metastatic site growth. Treatment of metastasizing (malignant) ameloblastoma should include close observation, thoracotomy with wedge resections, or experimental chemotherapeutic combinations., (Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of unknown etiology. Most patients present with lymph node involvement manifesting as adenopathy; however, RDD may arise primarily in a variety of extranodal sites, including bone. We report herein our experience with 15 cases of primary intraosseous RDD. The patients include 8 females and 7 males, who ranged in age from 3 to 56 (mean 27) years. The lesions arose in a variety of anatomical locations, including the tibia, femur, clavicle, skull, maxilla, calcaneus, phalanx, metacarpal, and sacrum. Radiographically, the lesions were lytic with well defined and usually sclerotic margins. Histologically, the lesions demonstrated the classic features of RDD and consisted of a mixed inflammatory infiltrate with numerous large histiocytes with abundant eosinophilic cytoplasm which exhibited emperipolesis. Some cases also contained numerous neutrophils. Immunohistochemical stains showed that the large histiocytes were S-100 positive. Follow-up information was available for 12 patients. Five patients eventually developed additional extraosseous manifestations, including testicular, lymph node, and subcutaneous lesions. One of these 5 also developed a new bony lesion within the sternum. One patient developed additional lesions within multiple bones of the hand and wrist, without extraosseous disease. One patient had stable bony lesions, whereas 5 remained disease free after treatment.

Objectives: Intraductal mucinous papillary neoplasm (IPMN) is being recognized with increasing frequency around the world. The true incidence, however, remains unknown. Our goal was to determine the incidence of IPMN in a population study., Methods: We used the records-linkage system of the Rochester Epidemiology Project to ascertain age- and sex-adjusted incidence rates of IPMN in Olmsted County, Minn, from January 1, 1984, to December 31, 2005. We also evaluated the number of prevalent cases as of December 31, 2005., Results: We identified 28 incident cases of IPMN. The age- and sex-adjusted cumulative incidence for IPMN in Olmsted County is 2.04 cases per 100,000 persons (95% confidence interval [CI], 1.28-2.80) from 1984 to 2005. Point prevalence on December 31, 2005, was 25.96 cases per 100,000 persons (95% CI, 14.53-37.38 cases) or 1 per 3852. Restricting to county residents 60 years and older, the point prevalence is 99.10 cases per 100,000 persons (95% CI, 54.40-143.79 cases) or one per 1009 persons. Thirty-two percent of patients were treated surgically. The 5-year survival rate after diagnosis was 59.6%., Conclusions: The incidence of IPMN in Olmsted County is low but increasing. Most patients do not die of complications related to the disease.

Aims and Background: HuR is a member of the family of ELAV (embryonic lethal abnormal vision)-like proteins that stabilize several cellular mRNAs by binding to AU-rich elements in the 3' untranslated region of the mRNA. Cyclooxygenase-2 (COX-2) is a well known enzyme that promotes tumor growth and metastasis. Recent studies have shown that HuR can stabilize the mRNA of COX-2, and cytoplasmic expression of HuR is associated with increased COX-2 expression in some cancers. The aim of this study was to investigate the correlation between COX-2 and HuR in Ewing sarcoma., Methods: The expression patterns for HuR and COX-2 were assessed via immunochemical analysis of 70 Ewing sarcoma samples., Results: Nuclear HuR expression was observed in 12 of 70 (17.1%) cases, but cytoplasmic expression was not observed. COX-2 expression was seen in 25 of 70 (35.7%) samples. Nuclear HuR and COX-2 were simultaneously expressed in 8 of 70 (11.4%) samples. The expression of nuclear HuR was significantly associated with COX-2 expression (P = 0.014). Neither HuR nor COX-2 expression showed a correlation with age or sex., Conclusions: COX-2 expression in Ewing sarcoma may not be directly related to mRNA stabilization by HuR. However, a correlation between COX-2 expression and nuclear HuR expression through indirect mRNA stabilization can be suggested.

Objective: USP6 rearrangements with several partner genes have been identified recently in primary but not in secondary aneurysmal bone cysts (ABCs). Several lesions show histologic features that may overlap with ABC, including myositis ossificans (MO), brown tumor, and cherubism. The objective of this study was to assess whether these lesions harbored USP6 rearrangements., Materials and Methods: Twelve patients with classic radiologic and histologic features of MO, 6 with brown tumors, and 5 with cherubism diagnosed at our institution were studied for the presence of USP6 rearrangements using fluorescence in situ hybridization with probes flanking the USP6 locus on chromosome 17p13. In addition, conventional cytogenetic analysis was performed in 2 patients with cherubism., Results: USP6 rearrangements were identified in 2 patients with radiologic and histologic features consistent with MO. None of the patients with brown tumor or cherubism demonstrated USP6 rearrangements. Cytogenetic analysis of the cherubism patients demonstrated normal karyotypes., Conclusion: These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements. In contrast, no USP6 rearrangements were found in patients with cherubism or brown tumor, supporting the prevailing view that these lesions are distinct biologic entities.

Background: Culturing of samples of periprosthetic tissue is the standard method used for the microbiologic diagnosis of prosthetic-joint infection, but this method is neither sensitive nor specific. In prosthetic-joint infection, microorganisms are typically present in a biofilm on the surface of the prosthesis. We hypothesized that culturing of samples obtained from the prosthesis would improve the microbiologic diagnosis of prosthetic-joint infection., Methods: We performed a prospective trial comparing culture of samples obtained by sonication of explanted hip and knee prostheses to dislodge adherent bacteria from the prosthesis with conventional culture of periprosthetic tissue for the microbiologic diagnosis of prosthetic-joint infection among patients undergoing hip or knee revision or resection arthroplasty., Results: We studied 331 patients with total knee prostheses (207 patients) or hip prostheses (124 patients); 252 patients had aseptic failure, and 79 had prosthetic-joint infection. With the use of standardized nonmicrobiologic criteria to define prosthetic-joint infection, the sensitivities of periprosthetic-tissue and sonicate-fluid cultures were 60.8% and 78.5% (P<0.001), respectively, and the specificities were 99.2% and 98.8%, respectively. Fourteen cases of prosthetic-joint infection were detected by sonicate-fluid culture but not by prosthetic-tissue culture. In patients receiving antimicrobial therapy within 14 days before surgery, the sensitivities of periprosthetic tissue and sonicate-fluid culture were 45.0% and 75.0% (P<0.001), respectively., Conclusions: In this study, culture of samples obtained by sonication of prostheses was more sensitive than conventional periprosthetic-tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection, especially in patients who had received antimicrobial therapy within 14 days before surgery., (Copyright 2007 Massachusetts Medical Society.)

Cardiac sarcoid is a rare and frequently fatal disease. We report a case of isolated cardiac sarcoid diagnosed during elective cardiac surgery. Although this patient presented with a history that was consistent with sarcoid heart disease, diagnosis is challenging when there is no other organ involvement with sarcoid. The patient was successfully treated with steroids and 8 years later remains clinically free of sarcoidosis.

Objectives: To present the classifications of malignant ameloblastomas, provide histopathologic guidelines for the diagnosis of ameloblastic carcinoma, and discuss treatment and long-term follow-up., Study Design: Fourteen archival specimens of ameloblastic carcinoma with detailed treatment and follow-up documentation were identified by the authors., Results: Traditional methods of microscopic observation form the basis for diagnosis. Histopathologic features of ameloblastic carcinoma include lack of differentiation, hypercellularity, high mitotic index, vascular invasion, and neural invasion., Conclusion: The long-term follow-up findings in this study support the concept that aggressive surgical intervention provides the best chance for survival. Patients treated otherwise had recurrence. The patients with the highest number of recurrences did not survive the disease.

Study Design: En bloc resection of a chordoma of the C5 vertebra with wide surgical margins., Objective: To present the surgical technique of total spondylectomy for a chordoma of the C5 vertebral body., Summary of Background Data: Malignant bone tumors require wide resection. Wide resection by total en bloc spondylectomy is difficult or not feasible for malignant vertebral tumors of the cervical spine due to the peculiar anatomic complexity of this region, including the vertebral arteries and the neural structures. There are no previous reports of en bloc resection of cervical spine tumors with wide surgical margins., Methods: Using staged posterior and anterior approaches, a total en bloc spondylectomy and spine arthrodesis was performed. En bloc excision of a C5 chordoma was achieved using a threadwire T-saw (Tomita and Kawahara, Kanazawa, Japan) with surgical margins free of tumor. The patient received postoperative adjuvant proton beam radiation therapy., Results: The patient remains disease-free 9 years after the operation., Conclusion: Total en bloc spondylectomy with wide surgical margins is feasible for malignant bone tumors of the cervical spine.

Osteoblastoma is an uncommon benign bone tumor most commonly located in the vertebral column or metaphysis of a long bone. Periosteal location is rare. We report a periosteal-based osteoblastoma, arising from the proximal tibia, in a 20-year-old woman who presented with knee swelling and pain of 2-year duration. Imaging studies showed a metaphyseal surface-based lesion with patchy radiodensities. The cortico-medullary junction was intact. The lesion was totally excised. Histopathologic evaluation disclosed immature bone and osteoid deposition in a vascularized stroma, associated with numerous osteoblasts and osteoclasts rimming the bony trabeculae. Plate-like arrangements of cartilage in the margin of the neoplastic tissue were also identified. At 16 months postoperatively, the patient was well without recurrence. Although extremely unusual, the presence of cartilage does not necessarily exclude the diagnosis of osteoblastoma.

Ewing sarcoma is a highly malignant tumor of bone preferentially arising in children and young adults. Its 5-year survival rate is only 50% despite the use of multimodal therapeutic approaches, requiring a search for new therapeutic targets and the development of novel therapeutic modalities. KIT and PDGFRs are type III receptor tyrosine kinases, and activating mutations in c-kit (which encodes KIT) and PDGFRs have been reported as oncogenic events in many malignancies. Imatinib is a selective inhibitor of KIT, PDGFR, and ABL tyrosine kinase activity and exerts different anti-tumor effects according to the regions of mutations in c-kit and PDGFR genes. Thus, we evaluated the immunohistochemical expression of KIT protein and the mutational status of exons 9, 11, 13, and 17 of the c-kit gene, exons 12 and 18 of the PDGFRA gene, and exon 12 of the PDGFRB gene in 71 formalin-fixed, paraffin-embedded Ewing sarcomas to increase our understanding of the potential, if any, of imatinib treatment for this malignancy. Of the 71 samples, 27 (38%) were immunohistochemically positive for KIT; however, activating mutations in c-kit were found in only 2 of 71 Ewing sarcomas (2.6%) within exon 9. No activating mutations in the PDGFRA and PDGFRB genes were found, but pleomorphism was identified in exon 18 of the PDGFRA gene. Our results for KIT protein expression agree with those of previous studies. This is the largest series of c-kit mutational analysis in Ewing sarcoma to date, and the results definitively show that c-kit activating mutations are not coincident with KIT protein expression in Ewing sarcoma in most samples. These findings imply other mechanisms for KIT activity and leave open the question of whether imatinib would be efficacious in the treatment of Ewing sarcoma.

The long-term outcome of periosteal osteosarcoma is not well defined. We sought to examine the disease-specific survival and risk of late recurrence or dedifferentiation in a cohort of 29 patients with average of 15.8 years followup. Disease-free survival was 83%, with five patients dying of disease at an average of 26 months after presentation. Survival was similar with respect to anatomic location, pathologic grade, and limb-salvage resection. All instances of local recurrence, metastatic disease, and death occurred within 3 years after presentation. There were no instances of dedifferentiation. Long-term disease-free survival is possible after resection of the local recurrence. Limb-salvage therapy seems to offer survival equivalent to amputation, and there does not seem to be a substantial risk of late recurrence, dedifferentiation, or disease progression.

Osteosarcoma is the most common primary bone sarcoma. Several studies published in the 1960s established that approximately one fifth of patients survive when treated with surgery alone. There is no information, however, about the long-term consequences of osteosarcoma. It is especially relevant to know if these patients are at risk for a second malignancy. We reviewed all clinical records from long-term (defined as more than 10 years) osteosarcoma survivors treated at Mayo Clinic in the prechemotherapeutic era from 1900 to 1960. We re-reviewed histological sections for most cases. Patients or next of kin provided follow-up information during telephone interviews. Rates of second malignancy were compared with expected rates in the population at large. We identified 465 patients treated for osteosarcoma. Of these patients, 83 (17.8%) were long-term survivors, including 19 who were alive up to 65 years after treatment. Of the 7 patients with pulmonary metastases, 3 died. A second malignancy developed in 26 patients, 15 of whom died of the malignancy. Although long-term survivors of osteosarcoma have a higher incidence of a second malignant tumor than a normal population, this increase was not statistically significant. No demographic or histological variables predicted long-term survival.

Unlabelled: To investigate outcome and identify prognostic factors, we retrospectively reviewed 24 consecutive patients with periosteal chondrosarcomas. There were 17 males and seven females with a mean age of 37.6 years (range, 15-73 years). The femur was involved in 12 patients, the proximal humerus in five, the tibia in two, and the distal fibula, ilium, pubis, metatarsal, and rib in one patient each. The mean greatest dimension of the lesions was 8.1 cm (range, 1.5-27 cm). Based on the histologic pattern, there were 18 Grade 1 tumors and six Grade 2 tumors. All patients were treated surgically. Two patients had intralesional excisions, five patients had marginal excisions, and 17 patients had wide resections. With a mean followup of 17 years (range, 28 months-47 years), seven of 24 patients (29%) had one or more local recurrences. The 5-year local recurrence-free survival was less in patients treated with intralesional or marginal excisions (25%) than for patients treated with wide resections (93%). At the latest followup, six of 24 patients (25%) had died of pulmonary metastases. The overall 5-year metastasis-free survival was 83%. The 5-year metastasis-free survival was less for patients with Grade 2 tumors (50%) than for patients with Grade 1 tumors (94%)., Level of Evidence: Therapeutic study, Level IV (case series no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Aims and Background: Id helix-loop-helix proteins function as regulators of cell growth and differentiation. However, they can induce malignant transformation when overexpressed. The EWS/ETS chimeric proteins in Ewing sarcoma act as aberrant transcription factors leading to tumorigenic processes. An enhanced expression of the Id2 gene in Ewing sarcoma cells was previously shown by gene array techniques. We investigated the expression of Id2 at the protein and gene level in Ewing sarcoma., Methods: We evaluated the expression of Id2 protein using immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a total of 71 cases of Ewing sarcoma. Additionally, a Ewing sarcoma cell line was examined by real-time quantitative PCR., Results: Id2 expression was observed in 65 cases (91.5%) of the 71 total cases examined and a high level of Id2 expression was observed in 45 of these cases (63.8%). In tumor cells, Id2 proteins displayed cytoplasmic as well as nuclear localization. The amplification of the Id2 gene was not noted in a Ewing sarcoma cell line using real-time quantitative PCR. The crossing points of Id2 in the Ewing sarcoma cell line, control fibroblast, and osteosarcoma cell line were 18.54 +/- 0.16, 18.25, and 18.34, respectively., Conclusions: Our data support a role for increased Id2 protein expression in Ewing sarcoma. However, this overexpression of the Id2 protein could not be confirmed by a corresponding change at the gene level in a Ewing sarcoma cell line.

Intraabdominal myositis ossificans (IMO) is a rare benign disorder characterized by reactive bone formation in intraabdominal soft tissue that should be distinguished from a malignant condition. We retrospectively searched our patient records and report 9 new cases of IMO. The lesions occurred in 7 men and 2 women with a mean age of 50 years (range, 24--76 years), 5 of whom had previous abdominal surgery. Histologically, all the cases were similar, consisting of a reactive mesenchymal process in adipose tissue. Mitosis was observed, but with no atypical forms, and the lesions lacked malignant cytologic features. IMO is an uncommon benign lesion that develops relatively rapidly. The pathogenesis is related to intraabdominal surgical procedures, but the exact mechanism remains to be determined., (Int J Surg Pathol 14(1):37-41, 2006.)

Unlabelled: Four children and six adults required en bloc resection of the lateral malleolus for malignant tumors. There were four osteosarcomas, three chondrosarcomas, two Ewing's sarcomas, and one adamantinoma. Surgical margins were wide in seven patients, marginal in two, and intralesional in one. A primary ankle arthrodesis was done in four adults and bracing without any reconstruction was done in four children and two adults. During a mean followup of 14.5 years (range, 3-30 years), there were two local recurrences (two of 10 patients) after a marginal excision and an intralesional excision. One patient had reoperation for a skip osteosarcoma lesion in the proximal fibula. Other complications included chronic osteomyelitis, a lateral talus subluxation and cavovarus deformity, and recurrent ankle instability and degenerative changes of the ankle. At the latest followup, all 10 patients showed no evidence of disease. Five patients who had primary or late ankle arthrodesis had a Musculoskeletal Tumor Society and International Society of Limb Salvage functional score of 28 points (92%), and two adolescents who had postoperative bracing alone had a functional score of 24 points (80%). The three remaining patients had a salvage amputation., Level of Evidence: Therapeutic study, Level IV (case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Objective: The purpose of this study was to evaluate the imaging features of desmoplastic fibroma of the bone, with an emphasis on MRI signal characteristics., Conclusion: Significant T2 shortening of a nonsclerotic fibroosseous lesion should place desmoplastic fibroma high among the diagnostic considerations.

Background: Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma., Methods: Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity., Results: Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment., Conclusions: Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma., ((c) 2004 American Cancer Society)

Objective: To review the imaging findings, age and gender distribution of chondroblastoma of the hands and feet., Design and Patients: Twenty-five cases of pathologically proven chondroblastoma of the hands and feet were reviewed. Available imaging modalities included radiographs (n=24), CT (n=3), MRI (n=5), and radionuclide bone scintigraphy (n=1). The following imaging features for each case were tabulated: location, presence of sclerotic margin, calcification, expansion, presence of fluid/fluid levels on cross-sectional imaging and surrounding edema on MRI. The images were evaluated for skeletal maturity using closure of the physeal plate in the region as a standard., Results: The average age at time of diagnosis was 23 years (range 7-57 years). Eighty-four percent (n=21) of the patients were skeletally mature. Males (20 of 25) outnumbered females by a ratio of 5:1. The bones of the foot accounted for 22 cases: calcaneus (n=8), talus (n=8), metatarsals (n=3), and the cuboid (n=3). The bones of the hand accounted for three cases: phalanx (n=1), triquetrum (n=1), and a metacarpal (n=1). Radiographically all lesions were osteolytic with identifiable calcification in 54% (13 of 24). Fluid/fluid levels were seen in four of five cases on MRI. Edema on MR images was seen in 40% (2 of 5). The size of the lesions ranged from 2 to 41 cm(2)., Conclusion: Chondroblastomas of the hands and feet share many of the radiographic characteristics seen in the long bones, but manifest in skeletally mature patients with a higher male to female ratio than in long bone chondroblastoma. Talar and calcaneal lesions were encountered only in males. Chondroblastoma of the wrist and hand appears to be exceptionally rare.

Objective: To determine the demographics, imaging findings, clinical symptoms, and prognosis of primary vertebral Ewing's sarcoma (PVES)., Design: A retrospective review of medical records and radiological studies of patients diagnosed with PVES from 1936 through 2001 in our institution and Department of Pathology consultation files was undertaken. Metastatic and soft tissue Ewing's sarcoma cases were excluded., Results: From a total of 1,277 cases of Ewing's sarcoma, 125 (9.8%) had a primary vertebral origin. There were 48 females and 76 males. Patient ages ranged from 4 to 54 (mean 19.3, standard deviation 10.7, median 16) years. Vertebral column distribution was four cervical (3.2%), 13 thoracic (10.5%), 31 lumbar (25%), and 67 sacrum (53.2%). More than one vertebral segment was involved in ten cases (8%). Satisfactory imaging studies were available in 51 patients: 49 radiographs, 27 computerized tomography (CT), and 23 magnetic resonance imaging (MRI) studies. The majority of tumors were lytic (93%). Three cases were mixed lytic and sclerotic (6%) and one sclerotic. In the nonsacral spine, the majority of lesions (12/20) involved the posterior elements with extension into the vertebral body. Five cases were centered in the vertebral body with extension into the posterior elements. Two cases were limited to the posterior elements, and one case solely involved the vertebral body. Ala was the most frequently affected site in the sacrum (18/26). Spinal canal invasion was frequent (91%). Detailed clinical information was available in 53 patients. Duration of symptoms ranged from 1 to 30 (mean 7) months. Local pain was the first symptom and seen in all cases. Neurological deficits were present in 21 (40%) cases. All patients received radiation in various dosages; 70% additionally received chemotherapy. Twenty-five patients had surgery, and two patients received bone marrow transplantation. Forty-five patients had follow-up; the five-year disease-free survival probability is 0.53. Disease-free survival probabilities are 0.60 for sacral tumors and 0.45 for nonsacral tumors., Conclusion: PVES is an uncommon tumor, usually seen in the second decade of life (mean age 19.3 years) with a male predilection (62%). An aggressive osteolytic lesion, particularly in the sacrum, should raise suspicion for this tumor in adolescents. Prognosis was similar in sacral and nonsacral tumors.

Up to 11% of chondrosarcomas may undergo regional anaplastic change, resulting in a high-grade noncartilaginous sarcoma arising within a typically low-grade chondrosarcoma. Known as dedifferentiated chondrosarcomas, these tumors are highly malignant with a very poor prognosis. The most important factor affecting survival is an accurate preoperative diagnosis. Therefore, the ability to predict the possibility of dedifferentiation in a malignant cartilage tumor on the basis of imaging findings is critical to ensure adequate tumor sampling at the time of biopsy. Imaging findings at radiography, computed tomography (CT), and magnetic resonance (MR) imaging in 174 patients with dedifferentiated chondrosarcoma were reviewed to determine whether there are radiologic features that can help predict dedifferentiation. On approximately one-third of the radiographs, one-third of the MR images, and one-half of the CT scans, the tumors demonstrated bimorphic features (ie, distinctly different tumor features juxtaposed within the lesion), most frequently a dominant lytic area adjacent to a mineralized tumor at radiography and a large, unmineralized soft-tissue mass associated with an intraosseous chondroid-containing tumor at CT and MR imaging. In the initial evaluation of patients with a primary bone tumor, thorough evaluation of the radiologic features of the entire tumor is critical., (Copyright RSNA, 2004)

To evaluate demographic and radiographic features that may differentiate between enchondroma and low-grade chondrosarcoma of the fibula. The radiographs of ninety-three histologically-confirmed cartilaginous tumors of the fibula were retrospectively reviewed along with demographic information as to patient age and gender. Fifty-four enchondromas and thirty-nine low-grade chondrosarcomas were included in the study. Multiple previously-established radiographic features distinguishing enchondroma from chondrosarcoma were evaluated in each fibular tumor in a consensus manner by two experienced, board-certified and fellowship-trained musculoskeletal radiologists. Five radiographic features were shown to statistically favor chondrosarcoma over enchondroma in the fibula. These were soft-tissue mass ( p<0.0001), periosteal reaction ( p=0.008), cortical disruption in the juxta-articular fibula ( p=0.0133), cortical thickening ( p=0.032), and tumor size greater than 4 cm ( p=0.0046). No statistically-significant demographic differences were found between patients with enchondroma and chondrosarcoma of the fibula. When two or more of the identified features of malignancy are identified in the same patient, chondrosarcoma is 2.4 times more likely than in those patients exhibiting none of the features of malignancy. Soft-tissue mass, periosteal reaction, cortical disruption in the juxta-articular fibula, cortical thickening, and tumor size greater than 4 cm indicate chondrosarcoma over enchondroma of the fibula. Radiographs demonstrating more than one of the identified malignant features are more likely to be due to chondrosarcoma than radiographs demonstrating none or only one of the identified features. No unique malignant features of chondrosarcoma in the fibula were observed when compared to previous descriptions of these tumors in the long and short tubular bones of the appendicular skeleton.

Purpose: To determine the age and gender distribution and imaging features of low-grade central osteosarcoma (LGCOS) of the long bones and pelvis and to discuss our findings in the context of lesions for which LGCOS has been mistaken., Materials and Methods: We reviewed 99 cases of LGCOS collected between 1919 and 2002 from our institution and pathology consultation files. Adequate imaging was available in 70 cases (36 radiographs only, 17 radiographs/CT, 12 radiographs/MRI, 2 radiographs/CT/MRI, 2 CT only, 1 MRI only, 5 bone scans)., Results: Patient average age was 30.1+/-14.2 years, with a slight female predominance. The femur and tibia were the most common long bones involved (29 and 20 each) with the majority of these tumors arising around the knee, followed by the fibula, radius, humerus and ulna (four, three, two and one case each). Flat bones were involved in six cases (three pelvis, one rib, two scapulae). Short tubular bones were involved in five cases (two metatarsal, two phalanges, one clavicle). The lesion extended to the end of the affected long bone in 22 of 59 cases. Lesions were large at presentation (mean 7.9+/-4.6 cm, range 2-24). Four radiographic patterns were identified: lytic with varying amounts of thick and coarse trabeculation ( n=22), predominantly lytic with few thin, incomplete trabecula ( n=21), densely sclerotic ( n=17) and mixed lytic and sclerotic ( n=10). Lesions were benign-appearing overall with focally aggressive features. CT or MRI demonstrated cortical breech or extension into the soft tissues in all cases., Conclusions: LGCOS has a variable appearance on radiographs. A frequent pattern is a slow-growing large intracompartmental fibro-osseous lesion with varying amounts of septal ossification associated with focal areas of aggression. A homogeneously sclerotic pattern was also noted. Imaging with CT or MRI was helpful in every instance in our series in identifying areas of soft tissue extension or cortical disruption suggestive of a low-grade malignancy.

Purpose: To evaluate patient age and sex and location and imaging appearances of primary vertebral osteosarcoma (PVOS) compared with histologic subtypes., Materials and Methods: Retrospective review (1915-2001) of imaging findings in patients with histologically proved primary osteosarcoma of vertebral column was performed. Two radiologists in consensus reviewed findings for location, origin site, matrix pattern, and spinal canal invasion and compared them with histologic subtypes. Radiation-induced, Paget, metastatic, and multifocal osteosarcoma were excluded., Results: Of 4,887 osteosarcoma cases, 198 (4%) were PVOS arising from vertebral column. There were 103 female and 95 male patients (age range, 8-80 years; median age, 34.5 years). Involvement included cervical (27 patients), thoracic (66 patients), lumbar (64 patients), and sacral (41 patients) spine. Adequate imaging findings were available in 69 patients, and involvement of two levels was seen in 12 (17%). In nonsacral spine, most tumors (44 cases) arose from posterior elements, with partial involvement of vertebral body. Lesions confined to vertebral body were less frequent (12 cases). Sacral tumors involved body and sacral ala. The most common histologic subtypes were osteoblastic (47 patients), chondroblastic (12 patients), telangiectatic (four patients), fibroblastic (four patients), small cell (one patient), and epithelioid (one patient). The majority (55 cases) demonstrated osteoid matrix mineralization; 17 showed marked mineralization. Five cases with marked mineralization were confined to vertebral body, with "ivory vertebra" appearance. Purely lytic pattern was seen in 14 (20%) cases. Lytic pattern was seen in four (100%) telangiectatic, three (75%) fibroblastic, three (25%) chondroblastic, three (6%) conventional osteoblastic, and one (100%) small-cell subtypes. Invasion of spinal canal was common (84% of cases). Appearance simulating osteoblastoma without soft-tissue mass was present (seven cases). Pathologic compression fractures were identified (seven patients)., Conclusion: This study provides age and sex distribution and location and imaging features in a large series of PVOS., (Copyright RSNA, 2004)

The expression of HER-2/neu has been proposed to be a prognostic indicator in osteosarcoma. To clarify the actual frequency of HER-2/neu expression in primary malignant cartilaginous tumors, we examined 89 cases comprising 17 conventional chondrosarcomas, 33 mesenchymal chondrosarcomas, and 39 clear cell chondrosarcomas. We used real-time PCR (LightCycler) assay to quantify the HER-2/neu gene status. The crossing point of HER-2 in normal control bone was 27.77. The crossing points of HER-2 in conventional, mesenchymal, and clear cell chondrosarcomas were 28.48+/-1.79, 27.74+/-3.02, 28.57+/-1.54, respectively. In conclusion, the amplification and overexpression of the HER-2/neu oncogene is absent or at least very rare in malignant cartilaginous tumors. The level of expression of HER-2/neu was similar in all cartilaginous tumor types.

The diagnostic value of combined radiology and fine needle aspiration cytology (FNAC) was retrospectively assessed in a consecutive series of 52 patients with high-grade osteosarcoma. The series was divided into typical and atypical osteosarcomas according to radiological features and site. Thirty-two of 33 radiologically typical osteosarcoma cases were correctly diagnosed by cytology; one lesion was diagnosed as sarcoma NOS. Nineteen osteosarcoma cases were radiographically atypical. Six of these were diagnosed as osteosarcoma and another six as sarcoma NOS. In three cases another type of sarcoma was suggested. One case was falsely classified as benign. FNAC of three cases were non-diagnostic. Overall, the diagnostic difficulties pertained to the radiologically atypical cases. Notably, four of these also posed considerable difficulties in the histopathological assessment prompting external consultation. Our study suggests that open biopsy can be obviated in high-grade osteosarcomas exhibiting typical radiological features, i.e., in two-thirds.

Amplification and overexpression of the HER-2/neu (c-erbB-2) oncogene have been observed in many cancers and are associated with a poor prognosis particularly in breast cancer. The human epidermal growth factor (HER)-2 receptor has recently been implicated in Ewing's sarcoma tumor cell line growth and chemosensitivity. The present study evaluates the amplification of HER-2/neu gene in paraffin sections from 42 cases of Ewing's sarcoma by a real-time quantitative polymerase reaction method using LightCycler system (Roche diagnostics, GmbH Mannheim, Germany). The relative copy number of HER-2/neu versus beta-globin was calculated at the crossing point. The mean calculated copy number in these cases of Ewing's sarcoma and normal controls was 26.43 and 26.93, respectively. The p value was 0.215 (p<0.05). Our results demonstrated an absence of HER-2/neu oncogene amplification in Ewing's sarcomas, and we suggest that HER-2/neu is not a biologically or therapeutically important pathway in Ewing's sarcoma.

Objective: To describe the imaging findings in eight cases of unilateral tensor fascia lata (TFL) hypertrophy presenting as soft tissue masses., Design: Imaging studies and medical charts of eight patients were reviewed retrospectively. The imaging studies included five radiographs, five computed tomography (CT) and six magnetic resonance imaging (MRI) examinations., Results: The majority of patients (seven of eight) presented with a palpable proximal anterior thigh mass. One patient was asymptomatic and incidentally diagnosed. There were six females and two males. Ages ranged from 27 to 86 years old (mean 61). MRI and CT showed unilateral enlargement of the TFL muscle in all cases., Conclusion: TFL muscle hypertrophy is an uncommon clinical entity, which can simulate a soft tissue tumor. The characteristic appearance on CT or MRI allows a confident diagnosis of muscle hypertrophy to be made, avoiding unnecessary biopsy or surgical intervention.

Mucoepidermoid carcinoma (MEC), a common malignant salivary gland neoplasm, is generally divided into low-, intermediate-, and high-grade types according to the histologic features. To our knowledge, the present report describes the first case of dedifferentiation occurring in a low-grade MEC. A 55-year-old man presented with a biphasic neoplasm of the right parotid gland composed of low-grade MEC and dedifferentiated high-grade anaplastic undifferentiated carcinoma. Immunohistochemically, carcinoembryonic antigen expression was restricted to the low-grade MEC portion. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade component. On image cytometric analysis, the low-grade MEC was diploid, whereas the dedifferentiated carcinoma was aneuploid. Although the patient was alive 10 years after the initial diagnosis, the tumor has recurred twice, at 3 months and 7 months after the initial resection. It is important to recognize that dedifferentiation can occur in a low-grade MEC, similar to other low-grade salivary gland carcinomas.

We investigated the expression and mutation of three isoforms of the Ras effector RASSF1 in 10 primary osteosarcomas and 6 osteosarcoma cell lines. RASSF1A was not expressed in 40% (4/10) of the primary osteosarcomas and 83.3% (5/6) of the osteosarcoma cell lines. RASSF1B and RASSF1C expression was absent in 30% (3/10) and 0% (0/10) of primary tumors, and 100% (6/6) and 0% (0/6) of osteosarcoma cell lines, respectively. Treatment of these cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine reactivated the transcription of RASSF1A, but not that of RASSF1B or RASSF1C. No somatic mutations were noted in RASSF1 in either the primary tumors or cell lines. Our data indicate that epigenetic inactivation of RASSF1A by hypermethylation of its promoter region is a frequent event, and may play an important role in the tumorigenesis of osteosarcomas.

Secondary chondrosarcomas are rare; recognition and diagnosis are difficult. Slow growth and late recurrence require long-term followup to understand the clinical course. In the current study, 107 patients had secondary chondrosarcoma arising in a solitary osteochondroma (61 patients) or multiple exostoses (46 patients). All histologic slides were reviewed without knowledge of the outcome, and radiologic studies were available for review in 71 cases. Patients with secondary chondrosarcoma were one to two decades younger than those with primary chondrosarcoma. Male preponderance and a predilection for flat bones were observed. The radiologic signs of sarcomatous degeneration included irregularity of the margin, inhomogeneous mineralization, and an associated soft tissue mass. The tumors generally were well-differentiated. Only 10 tumors were classified as Grade 2. Five-year and 10-year local recurrence rates were 15.9% and 17.5%, respectively, and 5- and 10-year mortality rates were 1.6% and 4.8% for patients having initial treatment at the authors' institution. Metastasis developed in five patients: in the lung in four patients and in the groin region in one patient. Most patients who died of tumor died of local recurrence. Wide excision had the lowest local recurrence rate. With successful surgical treatment, patients may have long-term disease-free survival.

Objective: The purpose of this study was to determine the age distribution, location, and imaging features of histologically proven solid variants of aneurysmal bone cysts in long tubular bones., Materials and Methods: We performed a retrospective review of imaging studies of histologically proven solid aneurysmal bone cysts in long bones between 1961 and 2001. There were 30 cases comprising 29 radiographic, six CT, and eight MR imaging examinations. The lesions were evaluated for bone involved, location within a long bone, matrix, size, soft-tissue mass, and MR imaging characteristics. The imaging findings were correlated with the histologic findings., Results: The patients were 17 females and 13 males ranging in age from 2 to 58 years (mean, 18 years). The bones involved were the femur (n = 10), the ulna (n = 7), the tibia (n = 7), the humerus (n = 2), the radius (n = 2), and the fibula (n = 2). The lesions were five juxtaarticular, 13 metaphyseal, one diametaphyseal, and 11 diaphyseal. The location was eccentric in 20 cases, of which two were intracortical and two periosteal, and central in 10. Lesion size varied between 1 and 7 cm. Thirty-three percent of lesions were nonaneurysmal. Four lesions were mineralized. A soft-tissue mass was present in four cases. Four lesions showed a permeative-lytic pattern simulating a malignant process. Unusual findings included periosteal reaction and development of a solid aneurysmal bone cyst in a preexisting fracture. MR imaging showed solid elements in all cases and pronounced edema in 50% of cases., Conclusion: Solid aneurysmal bone cyst is a reactive nonneoplastic bone lesion with varied imaging characteristics; one third of lesions are nonaneurysmal.

Background: A clinicopathologic study of 33 cases of plasma cell neoplasm of the jaw bones was performed., Methods: The Mayo Clinic's pathology files through 1995 were reviewed for cases of plasma cell neoplasia involving the jaw bones. Clinical data, radiologic features, and follow-up data were obtained from the hospitals of origin, referring physicians, and Mayo Clinic files. The histopathologic features of the 33 tumors were studied., Results: There were 21 (64%) male and 12 (36%) female patients, ranging in age from 25 to 81 years (mean, 57.7 years). Twenty-one tumors (64%) were classified as solitary plasmacytoma of bone (SPB) and 12 (36%) as multiple myeloma (MM). Among the SPB cases, 15 (71%) involved the maxilla, and 14 patients were men, with a mean age of 57.1 years. Abnormal serum protein was found in 22% of patients, and in nine patients (43%) the SPB converted to MM after a median of 20.7 months. Among the MM cases, seven (58%) affected the maxilla, seven patients were men with mean age of 58.3 years, and abnormal serum protein and Bence-Jones protein were found in 42% and 73% of the patients, respectively. Anaplastic histology was identified in seven (33%) SPB and six (50%) MM tumors, and amyloid was present in eight (38%) SPB and three (25%) MM tumors. Twelve (57%) SPB patients died of the disease after a median disease-free survival of 6.75 years, and the overall and disease-free survival rates at 5 and 10 years were 52%, 33%, 33%, and 24%, respectively. All MM patients died of the disease after a median survival of 17.6 months, and the 5-year and 10-year survival rates were 8% and zero. Eighty-six percent of the SPB patients with anaplastic histologic findings died of the disease (average survival, 3.8 years), whereas only 43% of those with classic histologic findings died of the disease (average survival, 11.75 years). Among MM patients, anaplastic histologic findings were associated with a 9-month average survival (26-month average survival for MM patients with classic histologic findings)., Conclusions: SPB patients seem to have a better prognosis than MM patients, and 43% of SPB tumors convert to MM after an average of 20.7 months. Anaplastic histologic findings seem to be associated with lower survival rates and periods for SPB patients and lower survival periods for MM patients., (Copyright 2003 Wiley Periodicals, Inc.)

Objective: To review the clinical and cytomorphologic features of 14 chordomas diagnosed by fine needle aspiration biopsy (FNAB) at our institution., Study Design: The cytology files from January 1985 to February 2000 at Mayo Clinic, Rochester, Minnesota, U.S.A., were searched for all cases diagnosed as chordoma by FNAB. Clinical, radiographic and cytomorphologic findings of each case were reviewed., Results: Ten males and four females (mean age, 55 years; range, 14-78) had tumors involving the sacrum (8), clivus (3) and vertebrae (lumbar, 2; cervical, 1). Pain was the presenting symptom in 11 patients. Most smears (82%) were cellular with a fibrillary background. Chondroid matrix was recognized in nine cases. Small, epitheliallike cells constituted the predominant cellular component in nine cases. Cells with clear, vacuolated cytoplasm were seen in almost 'every case; however, true physaliferous cells were rare. Mitotic figures were seen in four cases, binucleation in six and multinucleated giant cells in seven. Needle biopsies contained diagnostic material in all cases. Of the nine patients with follow-up (mean, 57 months; range, 3-184 months), three patients were alive and free of disease, five were alive with disease, and one was dead of disease at this writing., Conclusion: Because various cytologic presentations and overlapping cytologic features occur between chordoma, chondrosarcoma and metastatic clear cell carcinoma, it is important to recognize the various appearances of chordoma in FNAB.

Objective: To determine the age distribution, gender, incidence, and imaging findings of vertebral chondroblastoma, and to compare our series with findings from case reports in the world literature., Design and Patients: Case records and imaging findings of nine histologically documented vertebral chondroblastomas were retrospectively reviewed for patient age, gender, vertebral column location and level, morphology, matrix, edema, soft tissue mass, spinal canal invasion, and metastases. Our findings were compared with a total of nine patients identified from previous publications in the world literature. The histologic findings in our cases was re-reviewed for diagnosis and specifically for features of calcification and secondary aneurysmal bone cyst (ABC). Clinical follow-up was requested from referring institutions., Results: Nine of 856 chondroblastomas arose in vertebrae (incidence 1.4%; thoracic 5, lumbar 1, cervical 2, sacral 1). There were six males and three females ranging in age from 5 to 41 years (mean 28 years). Satisfactory imaging from seven patients revealed the tumor to arise from the posterior elements in four and the body in three. All tumors were expansive, six of seven were aggressive, and the spinal canal was significantly narrowed by bone or soft tissue mass in six. In one patient canal invasion was minimal. Calcification was pronounced in two and subtle in four. The sole nonaggressive-appearing tumor was heavily mineralized. Bony edema and secondary ABC were not seen on MR imaging. None of the cases had microscopic features of significant secondary ABC. Calcification, and specifically "chicken wire" calcification, was identified in two patients. Pulmonary metastases occurred in none., Conclusions: Vertebral chondroblastoma is a rare neoplasm that presents later in life than its appendicular counterpart. On imaging it is aggressive in appearance with bone destruction, soft tissue mass, and spinal canal invasion. The lesions contain variable amounts of mineral. Secondary aneurysmal cyst bone formation was not a feature in our study group.

Background: The aims of this study were to determine the rate of false-positive diagnosis with EUS-guided fine-needle aspiration and to identify factors contributing to this type of error., Methods: The records of 577 patients undergoing EUS-guided fine-needle aspiration were reviewed and a subset of 188 patients with malignant cytology who underwent surgery was identified. Operative histopathology was compared with EUS-guided fine-needle aspiration cytopathology and false-positive cases were identified. An experienced cytopathologist, who was not involved with the original interpretation of the specimens, reviewed these cases to identify any factor(s) contributing to the errors., Results: Three cases of false-positive diagnosis were identified (1.6%; 95% CI [0.3%, 4.6%]). By aspiration site, the false-positive rates were as follows: pancreas 2/39 (5.1%), 95% CI [0.6%, 17.3%]; lymph nodes 1/136 (0.7%), 95% CI [0.02%, 4.0%]; and other sites 0/13, 95% CI [0.0%, 24.7%]. In both instances of a false-positive diagnosis for a pancreatic aspiration cytologic specimen, interpretative errors were identified. The false-positive interpretation of cytologic material aspirated from a lymph node occurred in a patient without any evidence for malignancy at surgery. In 111 patients with confirmed esophageal, gastric, or rectal malignancy undergoing EUS-guided fine-needle aspiration of nonperitumoral lymph nodes, there was no false-positive diagnosis, suggesting that specimen contamination by luminal tumor is rare., Conclusion: The overall rate of false-positive diagnosis for EUS-guided fine-needle aspiration is similar to that reported for other modalities. Most false-positive diagnoses are caused by interpretation errors.

Chondroblastoma and chondromyxoid fibroma (CMF) has been investigated in numerous histological studies, but its biological nature and histogenetic origin are still a matter of debate. We evaluated the expression of type II collagen, S100A2, S100B, and osteocalcin to study the matrix biochemistry and phenotype of the neoplastic cells in these tumors. Immunohistochemically, the expression of type II collagen was diffuse in 15 cases (75%) among total 20 chondroblastomas and 12 (85.7%) among total 14 CMFs. The expression of S100B was also diffuse in all cases (100%) of chondroblastomas and 12 cases (85.7%) of CMFs. We were able to obtain the expression of S100A2, focally. The expression of osteocalcin was focally noted in 18 cases (90%) of chondroblastomas and 8 cases (57.1%) of CMFs. In conclusion, our data support that chondroblastoma and CMF are a distinct tumor entity with the basic expression of chondroid markers. But these tumors also show histologic diversity with focal co-expression of osteoid markers.

Well differentiated (low grade) osteosarcomas are often unrecognized and inadequately treated. We report on a patient with a well differentiated osteosarcoma of the tibia that radiographically presented with two strikingly dissimilar appearing juxtaposed lesions. Proximally, the lesion was sclerotic, and distally, osteolytic. The distal lytic half of the lesion showed focal cortical disruption on MR imaging. Microscopic correlation of the resected specimen suggested that the sclerotic component of the lesion had more fibrous dysplasia-like tissue with fewer features of well differentiated osteosarcoma, and the lytic component, features suggestive of well differentiated osteosarcoma. We believe this microscopic interpretation explains the disparate radiographic appearance as all belonging to well differentiated osteosarcoma with varying amounts of fibrous dysplasia-like tissue rather than the development of well differentiated osteosarcoma in fibrous dysplasia.

Mesenchymal chondrosarcomas are rare skeletal malignancies, which are typically characterized by tumor compartmentation. One tumor area is formed by small, undifferentiated neoplastic cells, whereas the second compartment is composed of cartilaginous areas. In this study, the application of in situ detection techniques enabled us to characterize the different tumor compartments according to their cellular differentiation patterns. The use of characteristic marker genes identified all steps of chondrogenesis within the different tumor compartments. Undifferentiated tumor cells in the small-cell areas were negative for vimentin and the cytoprotein S-100, whereas other tumor cells expressed collagen type IIA and vimentin indicating a chondroprogenitor cellular phenotype in these small-cell areas. Fully differentiated chondrocytic cells expressing collagen type II were found in the chondroid areas. The focal expression of type X collagen indicated hypertrophic differentiation of the neoplastic chondrocytes. The results characterize mesenchymal chondrosarcomas as skeletal malignancies that arise from undifferentiated chondroprogenitor cells and have the potential to undergo all steps of chondrocytic differentiation.

Cytogenetic studies of mesenchymal chondrosarcoma are few and to date, no specific or recurrent aberrations have been found. In this investigation, the cytogenetic and molecular cytogenetic (spectral karyotypic and fluorescence in situ hybridization) findings for two mesenchymal chondrosarcomas, one arising skeletally and the other extraskeletally, are reported. An identical Robertsonian translocation involving chromosomes 13 and 21 [der(13;21)(q10;q10)] was detected in both cases, possibly representing a characteristic rearrangement for this histopathologic entity. Both cases also exhibited loss of all or a portion of chromosomes 8 and 20 and gain of all or a portion of chromosome 12. The observation of similar chromosomal abnormalities in both skeletal and extraskeletal mesenchymal chondrosarcoma supports a genetic as well as histopathologic relationship between these anatomically distinct neoplasms.

Fibrosarcoma of bone is a relatively rare tumor; it accounts for less than 5% of bone sarcomas. The anatomical sites most commonly involved are the metaphyses of long tubular bones. Local pain, swelling, limitation of motion, and pathologic fracture are the common clinical signs and symptoms. Typical imaging findings include eccentrically located lytic lesions, with a geographic, moth-eaten, or permeative pattern of bone destruction, and extension into adjacent soft tissues. Surgery is the treatment of choice. The type of surgical procedure depends mainly on histologic grade, local conditions, and tumor location. With a high probability of metastases (>70%) after surgical treatment, perioperative adjuvant treatment modalities should be considered for high-grade tumors. The most important prognostic factors affecting survival include tumor grade, patient's age, and tumor location.