DOCSLIB.ORG

Extraskeletal Myxoid Chondrosarcoma: a Clinicopathologic, Immunohistochemical, and Ploidy Analysis of 23 Cases Andre M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Extraskeletal Myxoid Chondrosarcoma: a Clinicopathologic, Immunohistochemical, and Ploidy Analysis of 23 Cases Andre M Extraskeletal Myxoid Chondrosarcoma: A Clinicopathologic, Immunohistochemical, and Ploidy Analysis of 23 Cases Andre M. Oliveira, M.D., Thomas J. Sebo, M.D., James E. McGrory, M.D., Thomas A. Gaffey, M.D., Michael G. Rock, M.D., Antonio G. Nascimento, M.D. Department of Laboratory Medicine and Pathology (AMO, TJS, TAG, AGN) and the Department of Orthopedics (JEM, MGR), Mayo Clinic and Mayo Foundation, Rochester, Minnesota Extraskeletal myxoid chondrosarcoma (EMC) is a Twenty-three cases of extraskeletal myxoid chon- rare soft tissue sarcoma that was recognized as a drosarcoma, evaluated at the Mayo Clinic between distinct pathologic entity by Stout and Verner 1968 and 1996, were studied for clinicopathologic in 1953 (1). However, it was not until 1972 that features, immunohistochemical profile, Ki-67 activ- Enzinger and Shiraki (2) defined the clinicopatho- ity, and ploidy status to identify adverse prognostic logic features of EMC, showing a relatively pro- factors. Females and males were equally affected, tracted clinical course and a better prognosis than and the median age at diagnosis was 50 years. The that with conventional bone chondrosarcomas. tumors were located mainly in the lower extremities In 1992, Saleh et al. (3) reassessed the clinical (83%), and the median tumor size was 9.5 cm. Six- features of EMC in a series of 10 patients and teen tumors showed low cellularity (70%), and eight showed the “indolent but resilient” nature of this tumors had high mitotic activity (more than two per neoplasm; 7 of the patients died of tumor up to 17 10 high-power fields). The tumors were immunore- years after the initial diagnosis. Seven years later, active for vimentin (89%), synaptophysin (72%), ep- Meis-Kindblom et al. (4) studied a large series of ithelial membrane antigen (28%), and S-100 protein EMCs, most consultation cases, and showed that (17%). Nine tumors were diploid, three aneuploid, older age, larger tumor size, and proximal tumor and one tetraploid. Mean Ki-67 activity was 11% location were associated with decreased survival by (range, 1 to 45%). The 10-year overall survival rate multivariate analysis. was 78%. On univariate analysis, tumor size > 10 The histogenesis of EMC is still a subject of con- cm, high cellularity, presence of anaplasia or rhab- troversy. However, chondroblastic differentiation doid features, mitotic activity more than two per 10 has been supported by ultrastructural (5–15) and high-power fields, Ki-67 > 10%, and Ki-67 “hot histochemical (16–18) studies. In addition, cytoge- spot” > 25% were associated with decreased netic and molecular analyses have shown that EMC metastasis-free or overall survival. Ploidy status was is a distinct entity with the characteristic transloca- not associated with any adverse outcome. The pres- tion t(9;22) involving the EWS gene (22q12) and the ence of any of these adverse prognostic factors can TEC gene (9q22) in a majority of the cases (19–29). indicate the possibility of a more aggressive behav- We reviewed the clinicopathologic, immunohis- ior in extraskeletal myxoid chondrosarcoma, and a tochemical, and ploidy features in a series of 23 closer follow-up is suggested. cases of EMC evaluated at a single institution to identify potential prognostic factors associated with KEY WORDS: Extraskeletal myxoid chondrosar- a more aggressive behavior. coma, Immunohistochemistry, Ki-67, Ploidy, Prog- nostic factors. Mod Pathol 2000;13(8):900–908 MATERIALS AND METHODS Twenty-three patients in whom EMC was diag- nosed between 1968 and 1996 were included in this Copyright © 2000 by The United States and Canadian Academy of study. Eighteen patients with EMC were diagnosed Pathology, Inc. VOL. 13, NO. 8, P. 900, 2000 Printed in the U.S.A. and primarily treated at the Mayo Clinic, and five Date of acceptance: February 22, 2000. patients were referred by other institutions for ad- Address reprint requests to: A.G. Nascimento, M.D., Department of Lab- oratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905; ditional treatment or evaluation. Fifteen cases from e-mail: [email protected]. this series will be described in another article (30). 900 TABLE 1. Antibodies Used in This Study totic activity, anaplasia, spontaneous necrosis, and Antibody Type Source Dilution vascular invasion. Cellularity was defined as high Vimentin 3B4 M DAKO 1:500 when the neoplastic cells represented 75% or more Desmin Der11 M DAKO 1:100 (and the myxoid matrix represented 25% or less) of Wide-spectrum keratin P DAKO 1:200 Epithelial membrane antigen (EMA) M DAKO 1:20 the tumor area within the nodules in at least 25% of Polyclonal carcinoembryonic P DAKO 1:800 all slides evaluated per tumor. Mitotic count was antigen (pCEA) performed in 10 different high-power fields (HPF, S-100 protein P HSC 1:2,000 ϫ Synaptophysin SY38 M ICN Biomedicals 1:40 400 ) and reported as the number of mitotic fig- Chromogranin M Boehringer 1:1,000 ures per 10 HPF. Anaplasia was defined as the pres- Mannheim ence of enlarged and vesicular nuclei with promi- Leu-7 (CD57) M Becton Dickinson 1:20 Actin HHF35 (actin muscle-specific) M DAKO 1:50 nent nucleoli in at least 25% of the tumor area. ␣-Smooth muscle actin 1A4 M DAKO 1:150 Immunohistochemical studies were performed MIC2 (CD99) M DAKO 1:50 on 4-␮m-thick sections of 10% formalin-fixed, Glial fibrillary acid protein (GFAP) P DAKO 1:300 Ki-67 (MIB-1) M Immunotech 1:50 paraffin-embedded tumor material in 18 tumors, HSC, Hospital for Sick Children; M, monoclonal; P, polyclonal. according to the avidin-biotin-peroxidase complex system (31). Appropriate positive and negative con- trols were used for each antibody listed in Table 1. Clinical data, including follow-up information, Immunohistochemical analysis addressed the pres- were obtained from medical record review, refer- ence or absence of stain in a focal or diffuse pattern. ring physicians, and telephone survey. Focal reactivity was defined when less than 25% of Hematoxylin-eosin–stained archival slides from cells were reactive for a specific antibody. Immu- the primary tumors (5 to 21 slides per case; average, noreactivity intensity was not categorized. 13) were available for review in all cases. The main Digital image analysis was performed in 13 histologic features investigated were cellularity, mi- neoplasms according to a previously described TABLE 2. Clinical Features of Extraskeletal Myxoid Chondrosarcoma in 23 Patients Age Size Case Sex Location Cellularity Ploidy Treatment Follow-up and Outcome (yr) (cm)* 1 47 M Thigh, left 16 Low D WLE ϩ postRx Lung, sternum, vertebral mets (10 mo); DOD (23 mo) 2 29 M Thigh, left 18 Low D WLE ϩ postRx Lung mets (9 yr), DOD (22 yr) 3 34 M Mets to chest wall, mediastinum, 4† Low D ME ϩ postRx Knee tumor discovered (4.3 yr), and lungs (primary tumor: knee, alive (13 yr) right) 4 57 F Ankle, right 1.5 Low D WLE Alive, NED (21 yr) 5 27 M Ankle, left 10 High ... ME Alive, NED (6 mo) 6 63 F Thigh, right with mets to regional 4.5 Low ... WLE ϩ postRx Alive with mets (1 yr) lymph nodes and buttock 7 63 F Thigh, left 6 Low ... WLE Local recurrence (8 yr), alive with NED (20.3 yr) 8 42 F Thigh, right 9 Low ... WLE ϩ postRx Alive, NED (23.5 yr) 9 55 M Thigh, left 10 High A WLE Lung mets (4 mo), DOD (8 mo) 10 54 M Thigh, right 10 High T PreRx ϩ WLE Rib and vertebral mets (3.3 yr), DOD (6 yr) 11 50 F Shoulder, right 13.5 High D WLE ϩ postRx Lung mets (5.5 yr), DOD (6.8 yr) 12 22 F Shoulder, right 5 High ... WLE Alive, NED (14.6 yr) 13 49 F Leg, left 10 Low ... WLE Lung mets (1.2 yr), alive with mets (6.5 yr) 14 47 F Ankle, right 9 High A Amputation Alive, NED (8.2 yr) 15 38 F Chest wall with lung mets 5 High D PreChx ϩ WLE Alive with mets (7 yr) 16 52 M Thigh, right 11 Low ... WLE ϩ postRx Lung mets (4 yr), alive with mets (6.8 yr) 17 78 F Foot, right 5 Low D Amputation Alive, NED (5.5 yr) 18 48 M Foot, left 9 Low D Amputation Alive, NED (6 yr) 19 70 M Paravertebral area, left 5.5 Low A WLE ϩ postRx Alive, NED (6.2 yr) 20 71 M Thigh, left 18.5 Low ... PreRx ϩ WLE ϩ Local recurrence (3 mo), lung postRx mets (6 mo), alive with mets (3.3 yr) 21 61 F Knee, right 11 Low D WLE Local recurrence (4.8 yr), alive with NED (17 yr) 22 44 F Ankle, right 4 Low ... WLE Alive, NED (13 yr) 23 51 M Foot, left 6.5 Low ... Amputation Alive, NED (2 yr) A, aneuploid; D, diploid; ME, marginal excision; mets, metastasis; postRx, postoperative radiotherapy; preChx, preoperative chemotherapy; preRx, preoperative radiotherapy; T, tetraploid; WLE, wide local excision. * Greatest tumor dimension. † Knee tumor. Extraskeletal Myxoid Chondrosarcoma (A.M. Oliveira, et al.) 901 FIGURE 1. Characteristic multilobular architecture of extraskeletal FIGURE 3. Areas composed of large cells with vesicular nuclei and myxoid chondrosarcoma. This was present in all cases. prominent nucleoli were found in three tumors. Interestingly, two of these patients died of disease. FIGURE 2. Cords and strands of small eosinophilic cells immersed in a myxoid matrix. This is the classic histologic finding in extraskeletal FIGURE 4. High cellularity was present in 30% of cases and was myxoid chondrosarcoma. associated with decreased overall survival by univariate analysis. method (32). An average of 158 cells were neous population of cells with distinct biological counted per tumor (range, 53 to 213 cells).
Load more

Recommended publications
  • Dedifferentiated Extraskeletal Myxoid Chondrosarcoma of the Masticator Space - a Case Report
    The Korean Journal of Pathology 2011; 45(S1): S101-105 DOI: 10.4132/KoreanJPathol.2011.45.S1.S101 Dedifferentiated Extraskeletal Myxoid Chondrosarcoma of the Masticator Space - A Case Report - Geunyoung Jung · Kyung-Ja Cho We describe a 69-year-old woman who presented with a dedifferentiated extraskeletal myxoid Seung-Ho Choi1 · Mi-Jung Kim chondrosarcoma arising in the left masticator space. Computed tomography and magnetic reso- nance imaging revealed a 5 cm sized mass in the left masticator space. Histologically, the tumor Departments of Pathology and consisted of two distinct areas. The less cellular area was a low-grade extraskeletal myxoid chon- 1Otorhinolaryngology, Asan Medical Center, drosarcoma, composed of strands or cords of uniform spindle cells and abundant myxoid stro- University of Ulsan College of Medicine, Seoul, ma. The more cellular, dedifferentiated area corresponded to a high grade myxofibrosarcoma, Korea consisting of anaplastic tumor cells in myxoid stroma and geographic necrosis. The tumor cells of the former area were positive for S-100 protein, microtubule-associated protein-2 (MAP-2) and Received: October 25, 2010 class III β-tubulin, but negative for cytokeratin, smooth muscle actin, and desmin. The tumor cells November 23, 2010 Accepted: in the latter, pleomorphic area showed MAP-2 and β-tubulin immunoreactivity with a high Ki-67 Corresponding Author labeling index. Based on its histologic and immunohistochemical features, the tumor was consid- Mi-Jung Kim, M.D. ered a dedifferentiated extraskeletal myxoid chondrosarcoma. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea Tel: +82-2-3010-4557 Fax: +82-2-472-7898 E-mail: [email protected] Key Words: Extraskeletal myxoid chondrosarcoma; Cell dedifferentiation; Masticator space Extraskeletal myxoid chondrosarcoma (EMC) is a rare malig- CASE REPORT nant soft tissue sarcoma, distinguished from its skeletal coun- terpart by cytogenetic and histologic features.
    [Show full text]
  • Soft Tissue and Bone Tumors
    Soft tissue and bone tumors Zoltán Sápi MD, PhD 1st Department of Pathology and Experimental Cancer Research • Large and heterogeneous group with more than 200 entity and more than 50 sarcoma types • Previously: classified according to a histogenetic concept (fibrosarcoma from fibroblast) • Now: primitive multipotential stem cells differentiate along one or more lines Pluripotent mesenchymal stem cell, may differentiate into different direction lipogenic, neurogenic, fibro-myofibroblastic, smooth muscle, vascular, uncertain • Light microscopic evaluation (H&E) + many ancillary techniques Principles Characteristic morphology with corresponding biological behavior Variants (with the same biological behavior) Similar morphology but different biological behavior (MFS – LGFMS) Different morphology but the same genetic background (Giant cell fibroblastoma – DFSP) Genetic promiscuity (partly or totally) Molecular complexity complex karyotype Recurrent cytogenetic alteration, genetic instability Translocations fusion genes, proteins no fusion gene de novo formation de novo formation, rarely fusion gene is the initial step/driving force „dysplastic-precursors” synovial sarcoma, myxoid liposarcoma MPNST, leiomyosarcoma FISH probes Break-apart SS18 (SYT) Synovial sarcoma FOXO1 Alveolar rhabdomyosarcoma DDIT3 (CHOP) Myxoid liposarcoma FUS Myxoid liposarcoma, Angiomatoid fibrosus histiocytoma, LGFMS EWSR1 Ewing sc, AFH, DSRCT, EMC, MC, Clear cell sc EWSR1 COL1A1 Dermatofibrosarcoma protuberans USP6 Nodular fasciitis, Aneurysmal bone cyst ETV6 Infantile
    [Show full text]
  • Pathology and Genetics of Tumours of Soft Tissue and Bone
    bb5_1.qxd 13.9.2006 14:05 Page 3 World Health Organization Classification of Tumours WHO OMS International Agency for Research on Cancer (IARC) Pathology and Genetics of Tumours of Soft Tissue and Bone Edited by Christopher D.M. Fletcher K. Krishnan Unni Fredrik Mertens IARCPress Lyon, 2002 bb5_1.qxd 13.9.2006 14:05 Page 4 World Health Organization Classification of Tumours Series Editors Paul Kleihues, M.D. Leslie H. Sobin, M.D. Pathology and Genetics of Tumours of Soft Tissue and Bone Editors Christopher D.M. Fletcher, M.D. K. Krishnan Unni, M.D. Fredrik Mertens, M.D. Coordinating Editor Wojciech Biernat, M.D. Layout Lauren A. Hunter Illustrations Lauren A. Hunter Georges Mollon Printed by LIPS 69009 Lyon, France Publisher IARCPress International Agency for Research on Cancer (IARC) 69008 Lyon, France bb5_1.qxd 13.9.2006 14:05 Page 5 This volume was produced in collaboration with the International Academy of Pathology (IAP) The WHO Classification of Tumours of Soft Tissue and Bone presented in this book reflects the views of a Working Group that convened for an Editorial and Consensus Conference in Lyon, France, April 24-28, 2002. Members of the Working Group are indicated in the List of Contributors on page 369. bb5_1.qxd 22.9.2006 9:03 Page 6 Published by IARC Press, International Agency for Research on Cancer, 150 cours Albert Thomas, F-69008 Lyon, France © International Agency for Research on Cancer, 2002, reprinted 2006 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention.
    [Show full text]
  • Extraskeletal Myxoid Chondrosarcoma of the Left Buccal Mucosa
    ANTICANCER RESEARCH 32: 3345-3350 (2012) Extraskeletal Myxoid Chondrosarcoma of the Left Buccal Mucosa FRANCESCA ANGIERO Department of Surgical Science and Integrated Diagnostic, University of Genoa, Italy Abstract. Extraskeletal chondrosarcoma (ECS) is a rare lesions. Central chondrosarcomas are intramedullary in malignant neoplasm of bone or soft-tissue origin, characterized origin, although large tumors may erode the cortex and invade by the presence of spindle cells admixed with well- the surrounding soft tissue. Peripheral chondrosarcomas are differentiated cartilage or chondroid stroma. A case of ECS is subdivided into those secondary to a pre-existing reported in a 102-year-old woman who presented with a osteochondroma and those arising from the bone surface painful swelling of 2 cm in the left buccal vestibular area. (juxtacortical). Orthopantomography was insignificant. Biopsy and Histologically, they are subdivided into numerous types, histopathological examination revealed a tumor composed of including conventional intramedullary, clear cell, juxtacortical, an undifferentiated small round cell component that surrounded myxoid, mesenchymal, de-differentiated, and extraskeletal. a myxoid matrix of malignant cartilage. Immunohistochemical The conventional intramedullary chondrosarcoma is the most studies showed the tumor cells to be positive for nuclear S-100 frequent type, and most commonly involves the long bones or protein immunostaining, focally positive for vimentin and pelvis in up to 65% of cases. synaptophysin, and negative for epithelial membrane antigen, ECS are very rare neoplasms, less common than their desmin, chromogranin, Leu-7, glial fibrillary acid protein, actin intraosseous counterparts and represent approximately 2% of muscle-specific, cytokeratin, carcinoembryonic antigen, and all soft-tissue sarcomas (5-7). The histological types of CD99 (MIC2).
    [Show full text]
  • Bone & Soft Tissue
    14A ANNUAL MEETING ABSTRACTS and testicular atrophy with aspermatogenia (negative OCT3/OCT4 stain). There was 47 Comparison of Autopsy Findings of 2009 Pandemic Influenza evidence of acute multifocal bronchopneumonia and congestive heart failure. He carried A (H1N1) with Seasonal Influenza in Four Pediatric Patients two heterozygous mutations in ALMS1: 11316_11319delAGAG; R3772fs in exon 16 B Xu, JJ Woytash, D Vertes. State University of New York at Buffalo, Buffalo, NY; Erie and 8164C>T ter; R2722X in exon 10. County Medical Examiner’s Office, Buffalo, NY. Conclusions: This report describes previously undefined cardiac abnormalities in this Background: The swine-origin influenza A (H1N1) virus that emerged in humans rare multisystem disorder. Myofibrillar disarray is probably directly linked to ALMS1 in early 2009 has reached pandemic proportions and cause over 120 pediatric deaths mutation, while fibrosis in multiple organs may be a secondary phenomenon to gene nationwide. Studies in animal models have shown that the 2009 H1N1 influenza virus alteration. Whether and how intracellular trafficking or related signals lead to cardiac is more pathogenic than seasonal A virus, with more extensive virus replication and dysfunction is a subject for further research. shedding occurring the respiratory tract. Design: We report four cases of influenza A-associated deaths (two pandemic and two 45 Sudden Cardiac Death in Young Adults: An Audit of Coronial seasonal) in persons less than fifteen years of age who had no underlying health issues. Autopsy Findings Autopsy finding on isolation of virus from various tissue specimen, cocurrent bacterial A Treacy, A Roy, R Margey, JC O’Keane, J Galvin, A Fabre.
    [Show full text]
  • Ewing Sarcoma with Myxoid Stroma Case Report of an Unusual
    Pathology - Research and Practice 215 (2019) 152665 Contents lists available at ScienceDirect Pathology - Research and Practice journal homepage: www.elsevier.com/locate/prp Case report Ewing sarcoma with myxoid stroma: Case report of an unusual histological variant T ⁎ Borislav A. Alexiev , Farres Obeidin, Lawrence J. Jennings Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, 251 East Huron St, Feinberg 7-342A, Chicago, IL 60611, United States ARTICLE INFO ABSTRACT Keywords: We describe the case of a Ewing sarcoma with prominent myxoid stroma of the temporal bone in a 26-year-old Ewing sarcoma female. Histologically, the tumor exhibited a fascicular growth pattern of round to spindled cells with a minimal Myxoid variant amount of pale eosinophilic to clear cytoplasm and oval or spindled nuclei with finely dispersed chromatin and EWSR1-FLI1 fusion transcript small nucleoli. Myxoid changes were prominent (> 50%), with reticular or pseudoacinar growth of the loosely cohesive cells. The tumor showed strong expression of CD99, FLI1, and CD56 and was positive for the EWSR1- FLI1 fusion transcript. The diagnosis of Ewing sarcoma with myxoid stroma (myxoid variant) is particularly problematic owing to the large number of potential mimics. The tumor extends the morphologic spectrum of Ewing sarcoma beyond the previously described histological variants, and broadens the differential diagnosis. For any round/spindle cell sarcoma, prominent myxoid stroma and CD99 immunoreactivity should prompt consideration for molecular studies that include analysis of both EWSR1 and FLI1. 1. Introduction 2. Clinical history The Ewing sarcoma family of tumors (ESFT) is a group of malignant A 26-year-old female with no significant past medical history pre- small round blue cell tumors (SRBCT) that includes Ewing sarcoma (ES) sented to the neurosurgical clinic because of an incidentally discovered of bone, extra-osseous ES, primitive neuroectodermal tumors (PNET), right temporal bone lesion during a workup for headaches.
    [Show full text]
  • Myxoid Chondrosarcoma of Sphenoid Bone
    Published online: 2019-09-26 Case Report Myxoid chondrosarcoma of sphenoid bone Amit K Chowhan, Nandyala Rukmangadha, Rashmi Patnayak, Chandra Mouliswara Prasad Bodapati1, Vijaya Laxmi Bodagala2, Mandyam Kumaraswamy Reddy Departments of Pathology, 1Neurosurgery, 2Radiology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India ABSTRACT The myxoid variant of chondrosarcoma is usually seen in soft tissues where it is known as chordoid sarcoma or parachordoma. Rarely, it involves bone and when it does, cranial bones are the preferred location. This tumor is frequently amalgamated with the chondroid variant of chordoma, especially when the lesion occurs in the sphenoid bone/spheno-occipital region, because of their similar clinical presentations, anatomical locations, radiological findings, and mistaken histopathological features. It is essential to distinguish myxoid chondrosarcoma from the chondroid variant of chordoma, because of the different treatment protocol and prognostic importance. We present such a location-based diagnostic dilemma, solved successfully with ancillary immunohistochemistry. Key words: Chondrosarcoma, chordoma, immunohistochemistry, sphenoid bone Introduction 20 days. There was no history of hypertension, diabetes mellitus, or asthma. No source of any oral or respiratory Chondrosarcoma and chordoma of the skull base are rare infection was noted. She had no significant medical or tumors. The combined incidence is reported to be 0.03 per surgical history in the past. Computed tomography scan 100,000 persons in the United States.[1] The myxoid variant (CT scan) showed a lobular lesion measuring 3.9×3.0 cm of chondrosarcoma of bony origin is an uncommon entity with calcific specks in the medial temporal region and its location in the skull is rarer still with incidence as involving the left greater wing and body of the sphenoid low as 0.16%, including those arising from its coverings, bone along with the petrous part of the temporal supporting tissues, and cranial bones.[2] This tumor occurs bone.
    [Show full text]
  • INSM1 Expression and Its Diagnostic Significance in Extraskeletal Myxoid
    Modern Pathology (2018) 31, 744–752 744 © 2018 USCAP, Inc All rights reserved 0893-3952/18 $32.00 INSM1 expression and its diagnostic significance in extraskeletal myxoid chondrosarcoma Akihiko Yoshida1,2, Naohiro Makise1,3, Susumu Wakai1, Akira Kawai2,4 and Nobuyoshi Hiraoka1 1Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan; 2Rare Cancer Center, National Cancer Center Hospital, Tokyo, Japan; 3Department of Pathology, The University of Tokyo, Tokyo, Japan and 4Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan Extraskeletal myxoid chondrosarcoma is a rare subtype of sarcoma that affects the soft tissue and bones in middle-aged and elderly adults. Its diagnosis can be challenging, with the differential diagnoses including a wide variety of mesenchymal tumors. The line of differentiation of extraskeletal myxoid chondrosarcoma has been controversial, but recent evidence suggests a neuroendocrine phenotype. INSM1 is a zinc-finger transcription factor that plays a pivotal role in neuroendocrine differentiation, and has been proposed as a promising immunohistochemical marker of neuroendocrine carcinoma. The aim of this study was to determine the prevalence of INSM1 expression in extraskeletal myxoid chondrosarcoma and to understand its significance in sarcoma diagnosis. We immunostained the representative sections of 31 NR4A3-rearranged extraskeletal myxoid chondrosarcomas and 187 histological mimics. Nuclear staining of moderate or higher intensity in at least 5% of tumor cells was considered positive. Twenty-eight of the 31 extraskeletal myxoid chondrosarcomas (90%) were positive for INSM1, providing strong evidence for neuroendocrine differentiation. The staining was diffuse (450%) in 17 cases, with most immunopositive tumors showing at least focal strong expression.
    [Show full text]
  • Extraskeletal Myxoid Chondrosarcomas Do Not Show a Chondrocytic Phenotype
    Modern Pathology (2004) 17, 214–221 & 2004 USCAP, Inc All rights reserved 0893-3952/04 $25.00 www.modernpathology.org Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype Thomas Aigner1, Andre´ M Oliveira2,* and Antonio G Nascimento2 1Department of Pathology, University of Erlangen-Nu¨rnberg, Erlangen, Germany and 2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Extraskeletal myxoid chondrosarcoma is a rare mesenchymal soft-tissue malignancy of putative chondrocytic differentiation. Occasional overt cartilage formation, positivity for S-100 protein, and ultrastructural analysis have supported this view. However, most extraskeletal myxoid chondrosarcomas do not show chondroid tissue formation, and S-100 protein is found much less commonly than has been reported. Both these observations cast doubt on the histogenetic classification of extraskeletal myxoid chondrosarcoma as a chondroblastic entity. Mostly using matrix proteins as markers of mesenchymal cell differentiation, we investigated the biochemical matrix composition and cellular phenotype of the tumor cells in representative specimens from 14 extraskeletal myxoid chondrosarcomas. In all but one tumor specimen, which showed histomorphologically overt cartilage formation, only occasional staining for the proteoglycan aggrecan was found. Specimens from two tumors showed presence of collagen type II, and none was positive for collagen type X. Instead, collagen types I, III, and VI were diffusely positive. Also, S-100 protein was largely absent. Our results suggest that the basic cellular phenotype of extraskeletal myxoid chondrosarcoma is not chondrocytic or prechondrocytic and that extraskeletal myxoid chondrosarcoma is not a chondrosarcomatous entity. Extraskeletal myxoid chondrosarcoma consists most likely of primitive mesenchymal cells with focal, multidirectional differentiation. Chondrocytic differentiation is an unusual facet in the spectrum of differentiation patterns exhibited by these lesions.
    [Show full text]
  • Myxoid Chondrosarcoma in the Calcaneus: a Case Report with MR
    Skeletal Radiol (2007) 36: S82–S85 DOI 10.1007/s00256-006-0199-9 CASE REPORT Jong Won Kwon Myxoid chondrosarcoma in the calcaneus: Jung-Ah Choi Kyu-Sung Kwack a case report with MR imaging findings Joo Han Oh Jin Haeng Chung Heung Sik Kang Keywords Bone neoplasms . Received: 23 March 2006 J. H. Oh . Revised: 16 June 2006 Department of Orthopedic Surgery, Diagnosis MR Accepted: 2 August 2006 Seoul National University Published online: 12 January 2007 Bundang Hospital, # ISS 2007 Seong Nam, Gyeongi-Do, South Korea J. H. Chung Department of Pathology, J. W. Kwon . J.-A. Choi (*) . Seoul National University K.-S. Kwack . H. S. Kang Bundang Hospital, Department of Radiology, Seoul Seong Nam, Gyeongi-Do, South Korea National University Bundang Hospital, 300 Gumidong, Bundang-Gu, Seong Nam, Gyeongi-Do, 463-707, South Korea Abstract Skeletal myxoid chondro- e-mail: [email protected] Tel.: +82-31-7877609 sarcoma is an extraordinarily rare Fax: +82-31-7874011 neoplasm with a distinct histological morphology. Herein, we report a case J.-A. Choi . H. S. Kang of a myxoid chondrosarcoma in the Department of Radiology, Seoul National University calcaneus of a 20-year-old man with a College of Medicine, description of its MR imaging (MRI) Seoul, South Korea and histological findings. Introduction calcaneus, which is an unusual location for this tumor, with an emphasis on its radiological features, especially those that Myxoid chondrosarcoma of the bone is very rare. There are differentiate it from conventional chondrosarcoma. only a few references to this tumor in the literature. The most common location for skeletal myxoid chondrosarco- ma is the femur [1].
    [Show full text]
  • EWSR1—The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: an Updated Review
    diagnostics Review EWSR1—The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review Uta Flucke 1,2,*, Max M. van Noesel 2,3, Vasiliki Siozopoulou 4 , David Creytens 5 , Bastiaan B. J. Tops 2 , Joost M. van Gorp 6 and Laura S. Hiemcke-Jiwa 2 1 Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands 2 Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; [email protected] (M.M.v.N.); [email protected] (B.B.J.T.); [email protected] (L.S.H.-J.) 3 Division Cancer & Imaging, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands 4 Department of Pathology, Antwerp University Hospital, 2650 Edegem, Belgium; [email protected] 5 Department of Pathology, Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; [email protected] 6 Department of Pathology, St Antonius Hospital, 3435 CM Nieuwegein, The Netherlands; [email protected] * Correspondence: uta.fl[email protected]; Tel.: +31-24-36-14387; Fax: +31-24-36-68750 Abstract: EWSR1 belongs to the FET family of RNA-binding proteins including also Fused in Sarcoma (FUS), and TATA-box binding protein Associated Factor 15 (TAF15). As consequence of the Citation: Flucke, U.; van Noesel, multifunctional role of EWSR1 leading to a high frequency of transcription of the chromosomal region M.M.; Siozopoulou, V.; Creytens, D.; where the gene is located, EWSR1 is exposed to aberrations such as rearrangements. Consecutive Tops, B.B.J.; van Gorp, J.M.; binding to other genes leads to chimeric proteins inducing oncogenesis.
    [Show full text]
  • Development and Evaluation of a Pan-Sarcoma Fusion Gene Detection Assay Using the Nanostring Ncounter Platform
    The Journal of Molecular Diagnostics, Vol. 20, No. 1, January 2018 jmd.amjpathol.org Development and Evaluation of a Pan-Sarcoma Fusion Gene Detection Assay Using the NanoString nCounter Platform Kenneth T.E. Chang,*y Angela Goytain,z Tracy Tucker,x Aly Karsan,zx Cheng-Han Lee,zx{ Torsten O. Nielsen,zx{ and Tony L. Ngzx{ From the Department of Pathology and Laboratory Medicine,* KK Women’s and Children’s Hospital, Singapore, Singapore; the Duke-NUS Medical School,y Singapore, Singapore; the Department of Pathology,z University of British Columbia, Vancouver, British Columbia, Canada; the Department of Pathology,x British Columbia Cancer Agency, Vancouver, British Columbia, Canada; and the Department of Pathology,{ Vancouver General Hospital, Vancouver, British Columbia, Canada Accepted for publication September 22, 2017. The NanoString nCounter assay is a high-throughput hybridization technique using target-specific probes that can be customized to test for numerous fusion transcripts in a single assay using RNA from formalin- Address correspondence to fi fi Tony L. Ng, M.D., Ph.D., xed, paraf n-embedded material. We designed a NanoString assay targeting 174 unique fusion junctions Department of Pathology and in 25 sarcoma types. The study cohort comprised 212 cases, 96 of which showed fusion gene expression Laboratory Medicine, Vancou- by the NanoString assay, including all 20 Ewing sarcomas, 11 synovial sarcomas, and 5 myxoid lip- ver General Hospital, 855 W osarcomas tested. Among these 96 cases, 15 showed fusion expression not identified by standard clinical 12th Ave, Vancouver, BC V5Z assay, including EWSR1-FLI1, EWSR1-ERG, BCOR-CCNB3, ZC3H7B-BCOR, HEY1-NCOA2, CIC-DUX4, COL1A1- 1L3, Canada.
    [Show full text]