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Dedifferentiated liposarcoma with leukocytosis. A case report of G-CSF-producing soft-tissue tumors, possible association with undifferentiated liposarcoma lineage
Akio Sakamoto, Hiroshi Matono, Tatsuya Yoshida, Kazuhiro Tanaka, Shuichi Matsuda, Yoshinao Oda, Yukihide Iwamoto
World Journal of Surgical Oncology , 2007, DOI: 10.1186/1477-7819-5-131
Abstract: We report the case of a 72-year-old man with dedifferentiated liposarcoma characterized by dedifferentiated components of malignant fibrous histiocytoma (MFH)-like features in addition to well-differentiated lipoma-like liposarcoma, arising from his upper arm. Preoperative laboratory data showed leukocytosis (103,700/μl). The serum level of G-CSF was also elevated (620 pg/ml [normal, <8 pg/ml]). Nine days after the surgery, the leukocytosis was relieved (WBC; 6,920/μl) and the elevated serum G-CSF level was significantly decreased (G-CSF; 12 pg/ml). One month after the surgery, leukocytosis gradually began to appear again. Three months after the surgery metastatic lung lesions were confirmed, and the patient subsequently died of respiratory problems. In the English literature regarding soft-tissue tumors with leukocytosis, including the current case, we could review a total of 6 cases of liposarcoma with leukocytosis. The subtype of these 6 liposarcoma cases was undifferentiated liposarcoma, comprising dedifferentiated liposarcoma in 4 cases and pleomorphic liposarcoma in 2 cases.Since the only other soft-tissue tumor that was associated with leukocytosis was MFH, and since MFH is characterized by the absence of any specific differentiation, we would like to propose a possible association between G-CSF-producing soft-tissue tumors and an undifferentiated liposarcoma lineage, such as dedifferentiated liposarcoma or pleomorphic liposarcoma.Granulocyte-colony-stimulating factor (G-CSF) enhances differentiation along the neutrophil lineage, and accelerates maturation of metamyelocytes into mature neutrophils. Consequently, G-CSF is known to function as a hematopoietic growth factor and it is known to be responsible for leukocytosis. G-CSF-producing tumors associated with leukocytosis include various types of malignancies. In epithelial cancers, the expression of G-CSF has been associated with poor differentiation and invasiveness [1-3]. However, it is a rare event among
Dedifferentiated chondrosarcoma of the maxilla  [cached]
Munshi Anusheel,Atri Surinder,Pandey Kailash,Sharma M
Journal of Cancer Research and Therapeutics , 2007,
Abstract: A 20-year-old male reported with right-sided facial swelling, epistaxis and right sided proptosis of two months duration. Computerized tomography scan of the face revealed a mass in the right maxillary sinus. The patient underwent surgery and the postoperative histopathology was suggestive of dedifferentiated chondrosarcoma. The present report discusses this rare presentation and the issues in its management.
Putative Multifunctional Signature of Lung Metastases in Dedifferentiated Chondrosarcoma  [PDF]
Sergey Malchenko,Elisabeth A. Seftor,Yuri Nikolsky,Susan L. Hasegawa,Sean Kuo,Jeff W. Stevens,Stas Poyarkov,Tatiana Nikolskaya,Tamara Kucaba,Min Wang,Hakim Abdulkawy,Thomas Casavant,Jose Morcuende,Joseph Buckwalter,Raymond Hohl,Barry DeYoung,Kemp Kernstine,Maria de Fatima Bonaldo,Mary J. C. Hendrix,Marcelo B. Soares,Vera Maria F. C. Soares
Sarcoma , 2012, DOI: 10.1155/2012/820254
Abstract: Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma. We document for the first time a high heterogeneity of gene expression profiles among the individual lung metastases. Moreover, we reveal a signature of “multifunctional” genes that are expressed in all metastatic lung lesions. Also, for the first time, we document the occurrence of massive macrophage infiltration in dedifferentiated chondrosarcoma lung metastases. 1. Introduction Chondrosarcoma is the second most common malignant skeletal tumor. One of the subtypes of chondrosarcoma—dedifferentiated chondrosarcoma—is a high-grade pleomorphic noncartilaginous sarcoma, arising within a low-grade chondrosarcoma [1]. The median survival time for the dedifferentiated chondrosarcoma patients is 7.5 months [2]. Despite the fact that the process of metastatic dissemination depends upon a number of highly coordinated rate limiting steps [3, 4], it is remarkable that lung metastases develop within a few months of diagnosis in 90% of dedifferentiated chondrosarcoma patients. There is an increasing body of evidence pointing to the involvement of stem-like cells in the process of sarcoma’s metastatic dissemination [5–7]. In an attempt to elucidate the observed high frequency of dedifferentiated chondrosarcoma metastases, we developed a hypothesis that dedifferentiated chondrosarcoma-initiating cells might have some characteristics of stem-like cells. We further hypothesized that such dedifferentiated chondrosarcoma-initiating cells might exhibit at least two predominant features: multipotentiality, as one of the stem cell characteristics, which would explain pleomorphic histology of dedifferentiated chondrosarcoma [1, 8], and “multifunctionality”-expression of a set of “multifunctional” genes, which would explain fast progression of dedifferentiated chondrosarcoma through all the rate-limiting steps required for metastatic dissemination. Based on the hypothetical multipotentiality of dedifferentiated chondrosarcoma-initiating cells, we suspected that there would be a high degree of heterogeneity among metastases of a single patient. This would explain at least in part the notorious untreatability of dedifferentiated chondrosarcoma lung metastases.
Putative Multifunctional Signature of Lung Metastases in Dedifferentiated Chondrosarcoma  [PDF]
Sergey Malchenko,Elisabeth A. Seftor,Yuri Nikolsky,Susan L. Hasegawa,Sean Kuo,Jeff W. Stevens,Stas Poyarkov,Tatiana Nikolskaya,Tamara Kucaba,Min Wang,Hakim Abdulkawy,Thomas Casavant,Jose Morcuende,Joseph Buckwalter,Raymond Hohl,Barry DeYoung,Kemp Kernstine,Maria de Fatima Bonaldo,Mary J. C. Hendrix,Marcelo B. Soares,Vera Maria F. C. Soares
Sarcoma , 2012, DOI: 10.1155/2012/820254
Abstract: Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma. We document for the first time a high heterogeneity of gene expression profiles among the individual lung metastases. Moreover, we reveal a signature of “multifunctional” genes that are expressed in all metastatic lung lesions. Also, for the first time, we document the occurrence of massive macrophage infiltration in dedifferentiated chondrosarcoma lung metastases.
Dedifferentiated Peripheral Chondrosarcoma: A Review of Radiologic Characteristics  [PDF]
Eric R. Henderson,Elisa Pala,Andrea Angelini,Eugenio Rimondi,Pietro Ruggieri
Sarcoma , 2013, DOI: 10.1155/2013/505321
Abstract: Introduction. Peripheral de-differentiated chondrosarcomas are among the rarest malignant mesenchymal tumors. This tumor’s descriptive radiographic characteristics are reported but objective quantification does not exist. This investigation surveyed imaging of peripheral de-differentiated chondrosarcomas to facilitate better recognition of these uncommon tumors. Methods. Database interrogation for peripheral de-differentiated chondrosarcomas was performed; 23 patients were identified and imaging for 18 was reviewed. A musculoskeletal radiologist reviewed all studies for mineralization characteristics; presence of pre-existing osteochondromas; preserved corticomedullary continuity; adjacent cortical obliteration; soft-tissue mass; tumor necrosis; and presence of a cartilage cap. Tumor luminance was measured with computer software. Results. Mineralization was present in 17 tumors. Pre-existing exostoses were evident in nine cases, corticomedullary continuity was preserved in three cases. There was no difference in mineralization or other characteristics based on tumor location. Mean tumor luminance was 94.9?candela/m2. Conclusions. The imaging characteristics described for central de-differentiated chondrosarcomas are similar to the peripheral form of this tumor. Peripheral mineralization with a bimorphic pattern on CT scan and the presence of a soft-tissue mass should be considered worrisome for a peripheral de-differentiated chondrosarcoma, particularly in the setting of multiple hereditary exostoses. 1. Introduction Dedifferentiated chondrosarcoma is an uncommon tumor that is known to arise from preexisting, low-grade cartilage lesions [1–5]. This tumor demonstrates bimorphic histology with a well-differentiated cartilaginous component and a dedifferentiated, noncartilaginous component [4]. These lesions comprise approximately 11% of chondrosarcomas and generally occur in association with a central chondrosarcoma [3]. Because of its cartilaginous origin, dedifferentiated chondrosarcoma may also occur in the setting of a preexisting exostosis; however, the occurrence is rare [6]. When single-institution, redundant reporting is considered, approximately 60 discrete cases of peripheral dedifferentiated chondrosarcoma have been reported in limited series with an emphasis on descriptive reporting of histologic subtypes and patient survival [3, 4, 6–18]. A consistent radiographic appearance of conventional, central dedifferentiated chondrosarcoma is recognized and described [19]; as a result radiologists and surgeons trained in musculoskeletal imaging are
Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone  [cached]
van Oosterwijk Jolieke G,de Jong Danielle,van Ruler Maayke AJH,Hogendoorn Pancras CW
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-375
Abstract: Background Chondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce. Methods We developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential. Results We show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type. Conclusions Based on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies.
Dedifferentiated Chondrosarcoma with a High-Grade Mesenchymal Component Mimicking a Gastrointestinal Stromal Tumor  [PDF]
Toshihiro Akisue, Kenta Kishimoto, Teruya Kawamoto, Hitomi Hara, Masahiro Kurosaka
Open Journal of Pathology (OJPathology) , 2012, DOI: 10.4236/ojpathology.2012.23017
Abstract: This report presents a dedifferentiated chondrosarcoma with a unique pathologic feature. A 63-year-old man was referred with pain and a soft tissue mass in the left groin. A plain radiograph showed a mineralization in the proximal femur with partially osteolytic foci and an abnormal shadow in the soft tissue. Magnetic resonance imaging scans showed an inhomogeneous lesion with intermediate to partially low signal intensity on T1-weighted image and intermediate to high signal intensity on T2-weighted image. Microscopically, the tumor in the femur is a low-grade chondrosarcoma and the component of soft tissue was a high-grade sarcomatous lesion with an epithelial arrangement of tumor cells. A diffuse immunoreactivity to both vimentin and c-kit (CD117) antibodies was detected in the high-grade component. A dedifferentiated component is similar to those of gastrointestinal stromal tumor (GIST). This is the first case of dedifferentiated chondrosarcoma with a high-grade component mimicking a GIST.
Clinical outcome for patients with dedifferentiated chondrosarcoma: a report of 9 cases at a single institute  [cached]
Yokota Kazuya,Sakamoto Akio,Matsumoto Yoshihiro,Matsuda Shuichi
Journal of Orthopaedic Surgery and Research , 2012, DOI: 10.1186/1749-799x-7-38
Abstract: Background Dedifferentiated chondrosarcomas consist of two distinguishable components: low-grade chondrosarcoma components and high-grade dedifferentiated components. Materials and methods Nine cases (4 males, 5 females) of dedifferentiated chondrosarcoma were treated in our institute. The average age was 58.6 (range, 37–86) years. The tumor location was the long bone in 7 cases (femur, n=5; humerus, n=1; tibia, n=1) and the pelvic bone in 2 cases. The average time from appearance of symptoms to treatment was 9.4 (range, 1–40) months. Results and discussion On plain radiographs, matrix mineralization was seen in all 9 cases (100%). Bone destruction was observed in 5 of 9 cases (56%), while pathological fracture was seen in one femur case (11%). Lung metastasis was observed in all cases (initially in 5 cases; during the treatment course in 4 cases). Surgery was performed in 8 cases, with local recurrence occurring in 2 of those cases (time to recurrence, 2 and 10 months). Chemotherapy was administered in 4 cases, but did not result in significant improvement. All 9 cases died of lung metastases, with a median survival time of 10 (range, 3.4-18.8) months. The presence of initial metastasis at diagnosis was a significant unfavorable prognostic factor. Conclusion The prognosis of dedifferentiated chondrosarcoma is dismal. With the lack of convincing evidence of the benefit of chemotherapy, complete surgical excision is the initial recommended treatment.
Dedifferentiated chondrosarcoma arising in fibrous dysplasia: A case report and review of the current literature
Nicole MD Riddle,Hideko Yamauchi,Jamie T Caracciolo,David Johnson
Pathology and Laboratory Medicine International , 2009,
Abstract: Nicole MD Riddle1, Hideko Yamauchi2, Jamie T Caracciolo4, David Johnson2, G Douglas Letson2, Ardeshir Hakam1,3, Prudence V Smith1,2,3, Marilyn M Bui1,2,31Department of Pathology and Cell Biology, University of South Florida, Tampa, FL, USA; 2Department of Sarcoma, 3Department of Anatomic Pathology, 4Department of Radiology, Moffitt Cancer Center, Tampa, FL, USABackground: Fibrous dysplasia is an uncommon bone disease that has rare but clear potential for malignant transformation. The frequency is increased in polyostotic forms, McCune–Albright syndrome, Mazabraud’s syndrome, and previously irradiated sites. Rapidly progressing pain unrelated to trauma is the most concerning symptom. The early radiological features of sarcomatous transformation are moth-eaten or cystic areas of osteolysis, cortical destruction, and gradual formation of a soft tissue mass. The prognosis is unfavorable as most of the cases are in an advanced stage at the time of diagnosis.Methods: This case was diagnosed at a large cancer center in Florida. Pertinent clinical findings were obtained from chart review and inter-departmental consultation.Results: Histopathological examination revealed dysplastic lamellar bone with no osteoblastic rimming and “Chinese letter” shapes, areas composed of lobulated hyaline cartilage with mild to severe nuclear atypia, and areas of poorly differentiated cells with a spindled appearance, consistent with chondrosarcoma arising within fibrous dysplasia.Conclusions: Sarcomatous transformation of fibrous dysplasia is an uncommon occurrence, yet has significant importance for those with the disease. There may be difficulty with diagnosis given the symptoms and radiologic findings of benign fibrous dysplasia. We report a case of chondrosarcoma rising in fibrous dysplasia and review the current literature. This case is of interest due to the fact that the diagnosis of monostotic fibrous dysplasia was first made at the age of 59 and malignant transformation occurred within a decade with no history of trauma or radiation. This is an excellent example of how a change in symptoms without a history of trauma should be alarming to the clinician and warrants a thorough work-up for malignancy. To the best of our knowledge, this represents the second case of dedifferentiated chondrosarcoma within the English literature.Keywords: dedifferentiated chondrosarcoma, fibrous dysplasia, malignant transformation, McCune–Albright syndrome, Mazabraud’s syndrome
Dedifferentiated chondrosarcoma arising in fibrous dysplasia: A case report and review of the current literature
Nicole MD Riddle, Hideko Yamauchi, Jamie T Caracciolo, David Johnson, et al.
Pathology and Laboratory Medicine International , 2009, DOI: http://dx.doi.org/10.2147/PLMI.S5930
Abstract: ifferentiated chondrosarcoma arising in fibrous dysplasia: A case report and review of the current literature Case report (5366) Total Article Views Authors: Nicole MD Riddle, Hideko Yamauchi, Jamie T Caracciolo, David Johnson, et al. Published Date June 2009 Volume 2009:1 Pages 1 - 6 DOI: http://dx.doi.org/10.2147/PLMI.S5930 Nicole MD Riddle1, Hideko Yamauchi2, Jamie T Caracciolo4, David Johnson2, G Douglas Letson2, Ardeshir Hakam1,3, Prudence V Smith1,2,3, Marilyn M Bui1,2,3 1Department of Pathology and Cell Biology, University of South Florida, Tampa, FL, USA; 2Department of Sarcoma, 3Department of Anatomic Pathology, 4Department of Radiology, Moffitt Cancer Center, Tampa, FL, USA Background: Fibrous dysplasia is an uncommon bone disease that has rare but clear potential for malignant transformation. The frequency is increased in polyostotic forms, McCune–Albright syndrome, Mazabraud’s syndrome, and previously irradiated sites. Rapidly progressing pain unrelated to trauma is the most concerning symptom. The early radiological features of sarcomatous transformation are moth-eaten or cystic areas of osteolysis, cortical destruction, and gradual formation of a soft tissue mass. The prognosis is unfavorable as most of the cases are in an advanced stage at the time of diagnosis. Methods: This case was diagnosed at a large cancer center in Florida. Pertinent clinical findings were obtained from chart review and inter-departmental consultation. Results: Histopathological examination revealed dysplastic lamellar bone with no osteoblastic rimming and “Chinese letter” shapes, areas composed of lobulated hyaline cartilage with mild to severe nuclear atypia, and areas of poorly differentiated cells with a spindled appearance, consistent with chondrosarcoma arising within fibrous dysplasia. Conclusions: Sarcomatous transformation of fibrous dysplasia is an uncommon occurrence, yet has significant importance for those with the disease. There may be difficulty with diagnosis given the symptoms and radiologic findings of benign fibrous dysplasia. We report a case of chondrosarcoma rising in fibrous dysplasia and review the current literature. This case is of interest due to the fact that the diagnosis of monostotic fibrous dysplasia was first made at the age of 59 and malignant transformation occurred within a decade with no history of trauma or radiation. This is an excellent example of how a change in symptoms without a history of trauma should be alarming to the clinician and warrants a thorough work-up for malignancy. To the best of our knowledge, this represents the second case of dedifferentiated chondrosarcoma within the English literature.
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