Extraskeletal Chondrosarcoma

Background

These rare soft tissue tumors are related to chondrosarcomas of the bone by a similar histopathology. The majority of these tumors are classified as myxoid chondrosarcomas. Although the majority of the tumors present in the extremities, various organs around the body have reported cases.

EPIDEMIOLOGY CHARACTERIZATION

INCIDENCE Rare

AGE RANGE-MEDIAN Mean 52 years

SEX (M:F)
2:1

PATHOGENESIS CHARACTERIZATION

CHROMOSOMAL ABNORMALITIES

Extraskeletal Myxoid Chondrosarcoma With Neuroendocrine Differentiation A Pathologic, Cytogenetic, and Molecular Study of a Case With a Novel Translocation t(9;17)(q22;q11.2)

M. Harris, M.D.; J. Coyne, F.R.C.Path; M. Tariq, B.Sc.; B. P. Eyden, Ph.D.; M. Atkinson, F.R.C.Path; A. J. Freemont, M.D.; J. Varley, Ph.D.; C. Attwooll, B.Sc.; N. Telford, B.Sc.

From the Departments of Histopathology (M.H., B.P.E.), and Oncology Cytogenetics (M.T., N.T.), Christie Hospital, Manchester; the Department of Histopathology (J.C.), Withington Hospital, Manchester; the Department of Histopathology, Royal Oldham Hospital (M.A.); the Department of Osteo-articular Pathology, University of Manchester (A.J.F.); and the C.R.C. Department of Cancer Genetics (J.V., C.A.), Paterson Institute for Cancer Research, Manchester, U.K.

Am J Surg Pathol 2000;24:1020-1026 Abstract quote

A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was histochemical, immunohistochemical, and ultrastructural evidence of neuroendocrine differentiation is reported.

Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.

Translocation der(13;21)(q10;q10) in Skeletal and Extraskeletal Mesenchymal Chondrosarcoma.

Naumann S, Krallman PA, Unni KK, Fidler ME, Neff JR, Bridge JA.

Departments of Pathology and Microbiology (SN, PK, JRN, JAB), Orthopaedic Surgery (JRN, JAB), and Pediatrics (JAB), University of Nebraska Medical Center, Omaha, Nebraska.
Mod Pathol 2002 May;15(5):572-6 Abstract quote
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.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

Radiographs

CT scan and MRI

Extraskeletal mesenchymal chondrosarcoma.

Shapeero LG, Vanel D, Couanet D, Contesso G, Ackerman LV.

Department of Radiology, Institut Gustave-Roussy, Villejuif, France. .

Radiology 1993 Mar;186(3):819-26 Abstract quote

Among seven patients with extraskeletal mesenchymal chondrosarcoma (EMC), three children (aged 3-6 years) developed EMC in a central location and four adults (aged 38-54 years) developed EMC in both central and peripheral sites.

Conventional radiography and tomography and computed tomography (CT) depicted EMC as a soft-tissue mass with ring, arc, stippled, and highly opaque calcifications in four patients. Contrast-enhanced CT showed lobulation and peripheral tumoral enhancement, sometimes with central low-attenuation areas. On magnetic resonance (MR) images, EMC was a lobulated mass with high signal intensity on T2-weighted images and enhancement with low-signal-intensity focal areas on contrast-enhanced T1-weighted images. All adults developed recurrences and/or metastases and died. Of the three children, two were living and free of disease at the end of the study and the third child died of chemotherapeutic-induced leukemia.

Although imaging features of EMC are nonspecific, its chondroid-type calcifications and foci of low signal intensity within enhancing lobules may reflect its dual histopathologic morphologic characteristics of differentiated cartilage islands interspersed within vascular undifferentiated mesenchyme.

MRI of mesenchymal chondrosarcoma of the orbit: case report and review of the literature.

Shinaver CN, Mafee MF, Choi KH.

Department of Radiology, University of Illinois at Chicago Medical Center 60612, USA.
Neuroradiology 1997 Apr;39(4):296-301 Abstract quote
Extraskeletal mesenchymal chondrosarcoma is a relatively uncommon entity, an orbital location being extremely rare. A review of the literature revealed 16 reported cases of primary orbital mesenchymal chondrosarcoma demonstrated by plain film and CT. To the best of our knowledge, the MRI features of orbital extraskeletal mesenchymal chondrosarcoma have not been previously reported.

We present the case of an 18-year-old man with a 2-year history of progressive proptosis of the right eye who underwent CT, dynamic CT, MRI without and with gadolinium enhancement, and magnetic resonance angiography of the orbits. CT of orbital mesenchymal chondrosarcoma demonstrates a well-defined mass with multiple areas of fine and coarse calcification and shows moderate contrast enhancement. The noncalcified portions of the mass demonstrate signal intensity lower than or equal to gray matter on T1-weighted images and are isointense to the gray matter on T2-weighted images. Dynamic CT reveals delayed contrast enhancement. MRI has proven to be a valuable diagnostic tool in the diagnosis and differentiation of well-defined intraorbital masses.

By a combination of CT and MRI, it appears mesenchymal chondrosarcoma can be differentiated from other intraorbital lesions, such as cavernous hemangioma, hemangiopericytoma, orbital amyloidosis and fibrous histiocytoma.

Nuclear Medicine

Radionuclide imaging in extraskeletal myxoid chondrosarcoma.

Lin WY, Wang SJ, Yeh SH.

Department of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan.

Clin Nucl Med 1995 Jun;20(6):524-7 Abstract quote

The authors present a case of extraskeletal myxoid chondrosarcoma. The MR study clearly showed the extent of the tumor and a "rings and arcs" pattern appeared after Gadolinium-DTPA administration in the T1 weighted images. Dynamic Tc-99m MDP and Tc-99m DTPA scintigraphy showed increased blood flow in the mass. The delayed 3-hour images demonstrated moderate Tc-99m MDP uptake, but intense Tc-99m DTPA accumulation in the tumor. Surprisingly, the Ga-67 scan failed to demonstrate the tumor.

Laboratory Markers

CLINICAL VARIANTS CHARACTERIZATION

CAUDA EQUINA

Mesenchymal chondrosarcoma of the cauda equina.

Rushing EJ, Mena H, Smirniotopoulos JG.

Department of Pathology, University of Texas, Southwestern Medical Center at Dallas 75235-9072, USA.
Clin Neuropathol 1995 May-Jun;14(3):150-3 Abstract quote
Primary central nervous system mesenchymal chondrosarcomas are extremely rare tumors composed of primitive mesenchymal cells punctuated by islands of cartilage in various stages of differentiation. Although there are isolated reports of tumors arising in the spinal dura, to our knowledge extraskeletal mesenchymal chondrosarcoma localized to the cauda equina has not been reported in the literature.

We present an unusual case of a mesenchymal chondrosarcoma involving the nerve roots of the cauda equina. The clinical, pathological and neuroimaging features are reviewed and discussed.

INTRACRANIAL

Meningeal mesenchymal chondrosarcoma: report of 8 cases with review of the literature.

Scheithauer BW, Rubinstein LJ.
Cancer 1978 Dec;42(6):2744-52 Abstract quote
This paper reviews 8 personally examined cases of primary meningeal mesenchymal chondrosarcoma and 4 similar cases previously reported by others. The clinicopathologic features of these extraosseous intracranial and intraspinal examples are similar to those of other extraskeletal mesenchymal chondrosarcomas.

The tumor occurred most often in the second and third decades, showed a moderate tendency to local recurrence (5 of 12 cases) and occasionally metastasized to the lungs (1 case). Both intracranial and intraspinal tumors occurred with equal frequency, but the former, probably due to the later onset of symptoms, had the worse prognosis. Microscopically, they are composed of primitive undifferentiated mesenchymal cells and frequently well-defined islands of hyaline cartilage. There is an apparent correlation between the frequency of mitotic figures and the likelihood of recurrence and metastasis.

Electron microscopic study of one example revealed morphologic features similar to those previously described by others and supports the conclusion that the neoplastic cells represent primitive precartilaginous mesenchyme displaying focal cartilaginous differentiation.

Extraskeletal myxoid chondrosarcoma of the falx.

Salcman M, Scholtz H, Kristt D, Numaguchi Y.

Division of Neurological Surgery, University of Maryland School of Medicine, Baltimore.
Neurosurgery 1992 Aug;31(2):344-8 Abstract quote
Intracranial cartilaginous tumors are unusual lesions, of which myxoid chondrosarcoma is the rarest.

We describe this tumor arising from the falx in a 28-year-old woman treated at recurrence with a second operation and a radiation implant.

The behavior of classic chondrosarcoma and mesenchymal chondrosarcoma is also reviewed.

Intracranial extraskeletal mesenchymal chondrosarcoma: case report.

Bingaman KD, Alleyne CH Jr, Olson JJ.

Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Neurosurgery 2000 Jan;46(1):207-11 Abstract quote
OBJECTIVE AND IMPORTANCE: We present a patient with a dural-based intracranial extraskeletal mesenchymal chondrosarcoma, which was initially thought to be an atypical meningioma. This rare tumor should be considered in the differential diagnosis of young adults with an aggressive-appearing dural-based lesion.

CLINICAL PRESENTATION: A 21-year-old woman reported a 3-week history of severe headaches and intermittent nausea and vomiting. Neurological examination revealed right optic nerve swelling. Magnetic resonance imaging demonstrated a large, intensely enhancing extra-axial mass, which appeared to originate from the right side of the falx cerebri with significant mass effect. A presumptive diagnosis of meningioma was made.

INTERVENTION: The patient underwent preoperative embolization of the lesion and then underwent a bicoronal craniotomy, gross total resection of the tumor, removal of invaded calvarial bone, and cranioplasty. Pathological examination revealed an extraskeletal mesenchymal chondrosarcoma. Because of the potential for recurrence, the patient received subsequent radiotherapy. She remains free of recurrence 18 months after surgery.

CONCLUSION: Intracranial mesenchymal chondrosarcoma is a rare neoplasm that can mimic a meningioma radiographically. We present the first patient in whom this lesion has been documented with computed tomography, cardiography, magnetic resonance imaging, and pathological findings. We emphasize the importance of gross total resection and close follow-up for this potentially aggressive tumor, and we present a review of the literature.

KIDNEY

Mesenchymal chondrosarcoma of the kidney.

Malhotra CM, Doolittle CH, Rodil JV, Vezeridis MP.
Cancer 1984 Dec 1;54(11):2495-9 Abstract quote
A case of mesenchymal chondrosarcoma of the kidney, with osseous metastases, is presented in this article, and the clinical, radiologic, and histopathologic features of this uncommon neoplasm are discussed.

The addition of this case to those previously reported in the literature brings the total number of reported cases of mesenchymal chondrosarcoma of extraskeletal origin to 42. None of the previously reported cases originated from the kidney. The metastatic pattern of this case illustrates the propensity of mesenchymal chondrosarcoma to metastatize to unusual locations.

LABIA

Extraskeletal mesenchymal chondrosarcoma of the labium majus.

Lin J, Yip KM, Maffulli N, Chow LT.

Department of Clinical Oncology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Gynecol Oncol 1996 Mar;60(3):492-3 Abstract quote
Extraskeletal mesenchymal chondrosarcoma is a rare tumor. It has been noted to occur most commonly in muscle and the central nervous system. It has never been reported to occur in the soft tissues of the anogenital region.

We report the first such case, occurring in a 40-year-old woman who presented with a 1-year history of a mass originating in the left labium majus. After extensive local resection and lymph node dissection she remains disease free after 40 months follow-up.

LARYNX

Clear Cell Chondrosarcoma of the Larynx
A Case Report of a Rare Histologic Variant in an Uncommon Localization
B. Kleist, Ph.D.; M. Poetsch, Ph.D.; C. Lang, Ph.D.; A. Bankau, Ph.D.; G. Lorenz, Ph.D; K. Süess-Fridrich, Ph.D.; G. Jundt, Ph.D.; E. Wolf, Ph.D.

From the Institute of Pathology (B.K., G.L.), Institute of Forensic Medicine (M.P.), and the Department of Oto-Rhino-Laryngology (C.L., A.B.), Ernst-Moritz-Arndt-University, Greifswald, Germany; the Center of Bone Tumors of Swiss Society of Pathology (K.S.-F., G.J.), Institute of Pathology, University of Basel, Basel, Switzerland; and the Institute of Pathology (E.W.), Regional Hospital, Stralsund, Germany.
Am J Surg Pathol 2002;26:386-392 Abstract quote
The authors describe a clear cell chondrosarcoma of the larynx.

The clear cell type is a rare variant of chondrosarcoma that only twice has been reported in this localization. The light-microscopic diagnosis of the actual case was confirmed by immunohistochemical results, in particular by positive staining for S-100 protein and collagen type II, and ultrastructural findings. Loss of heterozygosity analysis demonstrated allelic loss at 9p22 and 18q21, but neither in the region of the Rb gene on chromosome 13q nor at the p53 locus on chromosome 17p where allelic loss has already been reported in chondrosarcomas.

Furthermore, our molecular genetic investigations revealed a methylation of the cell cycle control gene p16, which is localized on chromosome 9p. This characteristic has been recorded previously only in high-grade chondrosarcomas. Mutations in the exons of p16, alterations of the putative tumor suppressor gene MMAC1/PTEN on chromosome 10q, or an amplification of the cyclin D1 gene (CCND1) on 11q13, which were found to be changed in other studies of chondrosarcomas, could not be demonstrated here.

Chondrosarcoma of the larynx: a clinicopathologic study of 111 cases with a review of the literature.

Thompson LD, Gannon FH.

Departments of Endocrine and Otorhinolaryngic-Head & Neck Pathology and Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC, U.S.A.
Am J Surg Pathol 2002 Jul;26(7):836-51 Abstract quote
Chondrosarcomas of the larynx are rare tumors accounting for about 0.5% of all laryngeal primary tumors. A total of 111 laryngeal chondrosarcoma cases, diagnosed between 1970 and 1997, were retrieved from the Otorhinolaryngic-Head & Neck Tumor Registry of the Armed Forces Institute of Pathology.

There was a 3.6:1 male/female ratio of patients 25-91 years of age (mean, 64.4 years). Patients presented most frequently with hoarseness (n = 72 patients) present for a mean of 28.2 months. The majority of tumors involved the cricoid cartilage (n = 77) with a mean size of 3.5 cm. All tumors were invasive and malignant by radiology and/or histology (into bone within the ossified laryngeal cartilages in 52 tumors). Most tumors were low-grade lesions: grade 1 (n = 51), grade 2 (n = 54); there were six grade 3 tumors. An associated benign chondroma with (n = 41 tumors) or without ischemia (n = 24 tumors) was noted. All patients had surgery and five had radiation therapy. Wide excision or voice-sparing surgery was used in 73 patients, whereas 37 patients had a laryngectomy. Recurrences occurred in 20 (18%) patients, 10 of whom underwent salvage laryngectomy. At the last follow-up, 102 patients had no evidence of disease (alive or dead, mean 11.2 years) and five patients had evidence of disease (alive, one patient, 6.5 years; dead, four patients, mean 6.4 years).

The six patients with high-grade chondrosarcoma were all without disease at the last follow-up (mean, 15.1 years). There was no difference in clinical outcome based on grade (p = 0.210), location (p = 0.078), or treatment (p = 0.607) but was worse for patients with a myxoid-type chondrosarcoma (p = 0.044).

Primary laryngeal chondrosarcomas are typically low- to moderate-grade lesions involving the cricoid cartilage, frequently associated with a chondroma. They usually portend an excellent overall long-term prognosis with initial conservative voice-sparing surgery.

MEDIASTINUM

Extraskeletal mesenchymal chondrosarcoma of the mediastinum.

Chetty R.

Department of Anatomical Pathology, University of Cape Town, South Africa.
Histopathology 1990 Sep;17(3):261-3 Abstract quote
Extraskeletal mesenchymal chondrosarcoma is a rare tumour with a predilection for the meninges and lower limb, especially the thigh region.

This paper reports an extraskeletal mesenchymal chondrosarcoma occurring in the posterior mediastinum, a previously undocumented site.

ORBIT

Extraskeletal mesenchymal chondrosarcoma of the orbit.

Bagchi M, Husain N, Goel MM, Agrawal PK, Bhatt S.

Department of Pathology, King George's Medical College, Lucknow, India.
Cancer 1993 Oct 1;72(7):2224-6 Abstract quote
Mesenchymal chondrosarcoma, an uncommon lesion of bone and extraskeletal tissue, is rare in the orbit. A case of extraskeletal mesenchymal chondrosarcoma of the orbit in a 28-year-old woman presenting with proptosis and diminution of vision in the left eye is reported.

Histologically, the tumor showed areas of undifferentiated mesenchymal cells with islands of cartilage. Immunohistochemical analysis for S-100 protein showed focal positivity in chondroid areas. The eye was preserved and the patient has good vision after 2 years of follow-up.

Mesenchymal chondrosarcoma of the orbit. Report of three new cases and review of the literature.

Jacobs JL, Merriam JC, Chadburn A, Garvin J, Housepian E, Hilal SK.

College of Physicians and Surgeons, Columbia University, New York, New York.
Cancer 1994 Jan 15;73(2):399-405 Abstract quote
BACKGROUND: Extraskeletal mesenchymal chondrosarcoma is a rare tumor characterized by undifferentiated mesenchymal cells with islands of mature hyaline cartilage. Considering all sites, long-term survival is approximately 30%. Only seven cases of orbital mesenchymal chondrosarcoma have been reported.

METHODS: The records of three cases of orbital mesenchymal chondrosarcoma treated at the Columbia-Presbyterian Medical Center, and the seven previously reported cases of this tumor were reviewed to determine clinical characteristics and appropriate therapy.

RESULTS: Nine of the 10 patients were female; age of onset ranged from 10 to 35 years. Of eight patients with at least 2 years of observation, five survived 5 or more years after resection, or after resection plus adjuvant therapy. Two patients died of metastatic disease 2 and 5 years, respectively, after the initial treatment, and one died of pneumonia 6 months after surgery. Review of the histology of the three cases treated at Columbia-Presbyterian Medical Center did not identify distinct histologic types that might guide therapy. Presenting symptoms were typical of symptoms of an orbital mass: proptosis, pain, diplopia, change in visual acuity, ptosis, and tearing.

CONCLUSION: The small number of reported cases of mesenchymal chondrosarcoma of the orbit prevents definitive conclusions, but it appears that resection is adequate therapy in some cases. Extraskeletal mesenchymal chondrosarcoma of the orbit may have a better prognosis than tumors in other sites.

Mesenchymal extraskeletal chondrosarcoma of the orbit. Report of a case and review of the literature.

Khouja N, Ben Amor S, Jemel H, Kchir N, Boussen H, Khaldi M.

Service de Neurochirurgie, Institut National de Neurologie, Tunis, Tunisie.
Surg Neurol 1999 Jul;52(1):50-3 Abstract quote
BACKGROUND: Extraskeletal mesenchymal chondrosarcoma (MCS) is relatively uncommon. Orbital location is extremely rare: only 16 cases have been reported until now. We report a case of extraskeletal mesenchymal chondrosarcoma in a 27-year-old man and review the literature on its manifestations and management.

CASE REPORT: This patient had a 2-year history of progressive proptosis of the right eye. Skull X-ray and CT scan showed intraorbital calcification and a large lesion in the upper right orbit. He was operated three times because of recurrence of the tumor. The last recurrence was observed to have extension to the intracranial region, detected on MRI and CT scan. This secondary extension of the tumor to the intracranial region has not been previously reported. Immunohistochemical analysis for S-100 protein showed focal positivity.

CONCLUSION: Mesenchymal chondrosarcoma of the orbit is rare, and secondary extension to the intracranial region has not previously been reported.

Mesenchymal chondrosarcoma of the orbit: a clinicopathological study.

Kashyap S, Sen S, Betharia SM, Dada VK.

Departments of Ocular Pathology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All-India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Orbit 2001 Mar;20(1):63-67 Abstract quote
Extraskeletal mesenchymal chondrosarcoma of the orbit is a rare tumour and generally presents in young females.

We report the clinical presentation and histopathological features of a case of orbital mesenchymal chondrosarcoma in a middle-aged man. The prognosis of this tumour is poor and though rare it should be kept in the differential diagnosis of orbital masses.

PLEURA

Mesenchymal chondrosarcoma of the pleura.

Luppi G, Cesinaro AM, Zoboli A, Morandi U, Piccinini L.

Institute of Pathological Anatomy, University of Modena, Italy.

Eur Respir J 1996 Apr;9(4):840-3 Abstract quote
A 52 year old man developed an extraskeletal mesenchymal chondrosarcoma (ESMC) arising from the pleura. Clinically, the tumour mimicked a mesothelioma. Fine needle biopsy was consistent with the diagnosis of sarcomatoid mesothelioma.

Histological examination of multiple tumour samples, supported by immunohistochemical characterization, made it possible to correctly diagnose extraskeletal mesenchymal chondrosarcoma.

SINUS

Mesenchymal chondrosarcoma of the ethmoid sinus.

Takimoto T, Kato H, Yamashima T, Yamashita J, Umeda R.

Department of Otolaryngology, School of Medicine, Kanazawa University, Japan.
ORL J Otorhinolaryngol Relat Spec 1989;51(6):369-74 Abstract quote
Mesenchymal chondrosarcoma arising from primitive mesenchymal cells is a distinctive type of chondrosarcoma that exists in both skeletal and extraskeletal forms. The tumor is composed of undifferentiated cells with focal areas of cartilaginous or chondroid matrix. An extremely rare case of mesenchymal chondrosarcoma of the anterior and middle ethmoid sinuses in a 16-year-old girl is presented.

Magnetic resonance imaging provided more anatomic information about the tumor than computerized tomography and aided in surgical planning.

SOFT TISSUE

Primary extraskeletal mesenchymal chondrosarcoma in fossa poplitea of a 93-year-old woman.

Guschmann M, Melcher I.

Department of Pathology, Virchow Hospital, Humboldt University, Berlin, Germany.
Gen Diagn Pathol 1996 Oct;142(2):119-24 Abstract quote
We report the case of a 93-year-old female who had developed a primary extraskeletal chondrosarcoma in Fossa poplitea for many years. This rare, highly malignant tumor occurred in unusual location and at unusual age.

Histologically, it presented with sheets of primitive mesenchymal cells and islets of well-differentiated cartilaginous tissue. Immunohistochemical preparations revealed a positivity for neuron-specific enolase and vimentin, the cartilaginous portion of the tumor and isolated cells of the undifferentiated area also stained partially for S-100 protein.

Three years later, only one metastasis was found in the contralateral lower extremity.

HISTOLOGICAL TYPES CHARACTERIZATION

General

Extraskeletal myxoid chondrosarcoma: a reappraisal of its morphologic spectrum and prognostic factors based on 117 cases.

Meis-Kindblom JM, Bergh P, Gunterberg B, Kindblom LG.

Gothenburg Musculoskeletal Tumor Center, Sahlgren University Hospital, Department of Pathology, Gothenburg University, Sweden.

Am J Surg Pathol 1999 Jun;23(6):636-50 Abstract quote

Extraskeletal myxoid chondrosarcoma (EMC), a phenotypically and genotypically distinctive entity, has generally been viewed as a low-grade sarcoma. No studies regarding clinical and morphologic prognostic factors have been performed on a large series of cases with long-term follow-up because of the rarity and protracted clinical course of EMC.

The clinical, morphologic, and immunohistochemical features of 117 previously unreported cases were studied and statistically analyzed.

The male-to-female ratio was 2:1. The median patient age was 52 years (range, 6-89 years), and the median tumor size was 7 cm (range, 1.1-25 cm).

All tumors occurred within the deep subcutis or deeper soft tissues, with 80% occurring in the proximal extremities or limb girdles and 20% in the trunk. Most initial tumor excisions were intralesional or marginal.

Follow-up information was available in 99 cases (median, 9 years: range, 2 months-22 years). Forty-eight patients were disease-free, and 41 patients had evidence of disease (18 of these had died of disease). Ten additional patients survived, but their disease status was unknown.

There were local recurrences in 40 (48%) of 83 patients, 23 (58%) of whom had multiple local recurrences. Metastases occurred in 35 (46%) of 76 patients. The estimated 5-, 10-, and 15-year survival rates were 90%, 70%, and 60%, respectively.

All cases had histologic features characteristic of classical EMC, at least focally. Cellular foci devoid of myxoid matrix and reminiscent of chondroblastoma, Ewing's sarcoma, monophasic and poorly differentiated synovial sarcoma, fibrosarcoma, and rhabdoid tumor were identified in 29% cases. Older patient age, larger tumor size, and tumor location in the proximal extremity or limb girdle were adverse prognostic factors identified by multivariate analysis. Metastasis also adversely affected survival, although local recurrence did not.

This study shows that EMC has a unique clinical course, including a high rate of local recurrence, prolonged survival after metastasis in some cases, and eventually a high rate of death due to tumor. These features distinguish EMC from low-grade sarcomas.

This study shows that histologic grading is of no prognostic value in EMC because prognosis is dictated primarily by certain clinical features. Histologic recognition of classical EMC and cellular and solid, nonmyxoid variants is important, however, in view of EMC's distinctive biologic behavior.

Extraskeletal myxoid chondrosarcoma: A clinicopathologic, immunohistochemical, and molecular analysis of 18 cases

Sumika Okamoto, MD
Masanori Hisaoka, MD
Tsuyoshi Ishida, MD
Tetsuo Imamura, MD, etal

Hum Pathol 32:1116-1124. Abstract quote

Extraskeletal myxoid chondrosarcoma (EMCS) is an uncommon clinicopathologically well-defined tumor, but its pathogenesis and biologic behavior are poorly understood.

We reviewed 18 cases of EMCS to verify clinicopathologic features and immunohistochemical profiles together with molecular detection of the tumor-specific fusion genes.

The tumors were located mainly in the proximal extremities and limb girdles (72%). Two tumors arose at unusual anatomic sites: the finger and the hip joint. Nine of the 17 followed-up patients were alive and disease free, 4 were alive with recurrences and/or metastases, and 4 died of the tumor. Fifteen tumors showed typical features of EMCS, and 3 had hypercellular areas in addition to conventional EMCS areas. The tumors were variably immunoreactive for S-100 protein (50%), NSE (89%), peripherin (60%), and synaptophysin (22%). Chromogranin A and some epithelial markers (AE1/AE3, CAM5.2, and epithelial membrane antigen) were entirely negative. Frequent expressions of the neural/neuroendocrine markers suggest possible neural/neuroendocrine differentiation in at least some EMCSs, in addition to chondroid differentiation.

In a reverse-transcription polymerase chain reaction (RT-PCR) assay using paraffin-embedded specimens, EWS-CHN or TAF2N-CHN fusion gene transcripts characteristic of EMCS could be detected in 15 (83%) of the 18 cases: EWS-CHN type 1 in 11 cases, EWS-CHN type 2 in 1, and TAF2N-CHN in 3. Three fusion-negative cases included 2 conventional EMCSs and 1 considered a �cellular� variant of the tumor. None of 30 other soft tissue and bone tumors with myxoid or chondroid morphology that we examined contained these fusion genes.

Thus, RT-PCR detection of EWS-CHN or TAF2N-CHN fusion gene using archival paraffin-embedded tissue is a feasible and useful ancillary technique for the diagnosis of EMCS.

VARIANTS

RHABDOID FEATURES

Extraskeletal Myxoid Chondrosarcoma with Rhabdoid Features, with Special Reference to Its Aggressive Behavior.

Oshiro Y, Shiratsuchi H, Tamiya S, Oda Y, Toyoshima S, Tsuneyoshi M.

Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University.

Int J Surg Pathol 2000 Apr;8(2):145-152 Abstract quote

The presence of rhabdoid cells has been reported in various types of malignant neoplasms. Thirty-six cases of extraskeletal myxoid chondrosarcoma (EMC) were reviewed, and three of them revealed rhabdoid features. These cases contained cells having prominent eosinophilic globular cytoplasm, but were otherwise typical of EMC. Immunohistochemically, cytokeratin (CAM 5.2) was positive in three of 20 cases (15%), including two of the three with rhabdoid features. The rhabdoid cells were also immunostained with vimentin. The 5-year survival rate in the 26 cases with follow-up information was 73%, and the 10-year survival rate was 63%. The cases with rhabdoid features had a significantly poorer prognosis (p=0.0271).

This study suggests that presence of rhabdoid features is a predictor of aggressive behavior in EMC, as it was shown to be in other mesenchymal neoplasms.

HIGH GRADE HISTOLOGY

High-grade extraskeletal myxoid chondrosarcoma: a high-grade epithelioid malignancy.

Lucas DR, Fletcher CD, Adsay NV, Zalupski MM.

Department of Pathology, Wayne State University School of Medicine, Harper Hopspital and Karmanos Cancer Center, Detroit, MI, USA.

Histopathology 1999 Sep;35(3):201-8 Abstract quote

AIMS: Extraskeletal myxoid chondrosarcoma is typically a low-to-intermediate grade sarcoma that is associated with a prolonged clinical course. High-grade forms are rare and not well characterized. In this series we report the clinicopathological, immunohistochemical and ultrastructural findings in four cases of high-grade extraskeletal myxoid chondrosarcoma.

METHODS AND RESULTS: The patients were three men and one woman (ages 34-73 years) with tumours located in the thigh (two cases), paraspinal soft tissue and perineum. Three patients had metastases, one at 12 weeks, one at 10 months, and one at presentation of recurrent tumour. In the latter case the original tumour was low grade and became high grade when it recurred 3.5 years later. All three patients died of disease. One patient was lost to follow-up. The most striking histological feature in all four tumours was the presence of numerous large epithelioid cells. These cells were arranged in cords within myxoid matrix and in sheets devoid of matrix. Two tumours had areas of conventional extraskeletal myxoid chondrosarcoma intermixed with the high-grade areas. One tumour showed transition to high-grade spindle cell sarcoma. One tumour had cells with rhabdoid features. Immunohistochemically, two tumours focally expressed S100 protein, and one focally expressed EMA. All were negative with cytokeratin, desmin, smooth muscle actin, HMB45, CD31 and CD34. Ultrastructural features in three cases were compatible with chondrosarcoma; one tumour had aggregates of microtubules within rough endoplasmic reticulum, a characteristic feature of this tumour.

CONCLUSIONS: High-grade extraskeletal myxoid chondrosaroma is a rare and aggressive soft tissue sarcoma, and should be included in the differential diagnosis of other epithelioid malignancies.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

IMMUNOPEROXIDASE S100+
EMA+/-

ELECTRON MICROSCOPY

An ultrastructural study of extraskeletal mesenchymal chondrosarcoma.

Sato N, Minase T, Yoshida Y, Narimatsu E, Muroya K, Asaishi K, Kikuchi K.
Acta Pathol Jpn 1984 Nov;34(6):1355-63 Abstract quote
A rare case of extraskeletal mesenchymal chondrosarcoma in a 47-year-old woman is reported. The tumor was located in the soft tissue of left upper arm without any involvement of the humerus. The outer portion of the tumor was histologically composed of primitive mesenchymal cells, and the inner portion showed zones of cartilaginous differentiation.

Ultrastructurally, the tumor cells in the primitive areas had a relatively small number of mitochondria, rough endoplasmic reticulum, and free polysomes, and the matrix of the tumor consisted of dense bundles of collagen fibrils. The cartilaginous cells seen in the central portion of tumor were embedded in the matrix of abundant collagen fibrils and matrix granules. They had polysomes, well-developed Golgi complexes, and ample rough endoplasmic reticulum frequently with dilatation. Clear zones adjacent to the cells were seen in the extracellular matrix.

With a review of the literature, the histogenesis of this particular tumor is discussed.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Chondroblastoma

Ewing's sarcoma

Fibrosarcoma

Hemangiopericytoma

Malignant hemangiopericytoma and other sarcomas with hemangiopericytoma-like pattern.

Tsuneyoshi M, Daimaru Y, Enjoji M.
Pathol Res Pract 1984 May;178(5):446-53 Abstract quote
This clinicopathologic study concerns 19 cases of malignant hemangiopericytoma among 755 cases of soft tissue sarcomas. The age of the patients ranged from 18 to 76 years, with a median of 43 years. Tumors occurred on the trunk in 8, lower extremities in 5, the head in 3, and the retroperitoneum in 3. According to follow-up information, nine of the 19 patients had died.

Histologically the tumor was characterized by its homogeneous vascular pattern, its uniform cell population and a wide range of cellular anaplasia. After extensive sampling of the tumors, a comparative light microscopy revealed differences in diagnostic histology between malignant hemangiopericytoma and other soft tissue sarcomas with a hemangiopericytoma-like vascular pattern.

The frequency of appearance of such pericytoma pattern in different soft tissue sarcomas was as follows: 4/4 cases (100%) in extraskeletal mesenchymal chondrosarcoma, 11/14 (79%) in infantile fibrosarcoma, 27/45 (60%) in synovial sarcoma, 62/201 (30%) in malignant fibrous histiocytoma, 9/37 (25%) in malignant schwannoma and 6/72 (8%) in liposarcoma.

Rhabdoid tumor

Synovial sarcoma

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

Extraskeletal myxoid chondrosarcoma. A clinicopathologic study of ten patients with long-term follow-up.

Saleh G, Evans HL, Ro JY, Ayala AG.

Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

Cancer 1992 Dec 15;70(12):2827-30 Abstract quote

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma that has been reported to have a relatively good prognosis.

The authors report ten patients with EMC on whom there was a minimum follow-up of 10 years.

The patients' ages ranged from 31 to 72 years (mean, 57 years); there were six men and four women (seven white, three black). The tumor locations included the knee area and thigh (three patients each), the shoulder (two patients), and the leg and foot (one patient each). The tumors ranged from 3.5 to 18 cm in greatest dimension (median, 11.5 cm). All cases had typical histologic features. Lung metastases developed in all patients but one, and three patients had extrathoracic metastases (one in regional lymph nodes; one in subcutis; and one widespread). Four of the patients who had metastases also had local recurrence, as did the only patient without known metastases. Seven patients died of tumor at 4, 5, 8, 10, 15, 16, and 17 years, respectively, and the three remaining patients were alive with metastatic disease at latest follow-up of 13, 14, and 16 years. The authors' results are distinctly different from those previously reported in series with shorter follow-up times.

The authors conclude that extraskeletal myxoid chondrosarcomas are indolent but resilient and capricious tumors with a high potential for metastasis, especially to the lungs, over the long-term.

Am J Surg Pathol 1999 Jun;23(6):636-50

Estimated 5-, 10-, and 15-year survival rates were 90%, 70%, and 60%, respectively.

Extraskeletal myxoid chondrosarcoma: a clinicopathologic, immunohistochemical, and ploidy analysis of 23 cases.

Oliveira AM, Sebo TJ, McGrory JE, Gaffey TA, Rock MG, Nascimento AG.

Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA

Mod Pathol 2000 Aug;13(8):900-8 Abstract quote

Twenty-three cases of extraskeletal myxoid chondrosarcoma, evaluated at the Mayo Clinic between 1968 and 1996, were studied for clinicopathologic features, immunohistochemical profile, Ki-67 activity, and ploidy status to identify adverse prognostic factors.

Females and males were equally affected, and the median age at diagnosis was 50 years. The tumors were located mainly in the lower extremities (83%), and the median tumor size was 9.5 cm. Sixteen tumors showed low cellularity (70%), and eight tumors had high mitotic activity (more than two per 10 high-power fields). The tumors were immunoreactive for vimentin (89%), synaptophysin (72%), epithelial membrane antigen (28%), and S-100 protein (17%). Nine tumors were diploid, three aneuploid, and one tetraploid. Mean Ki-67 activity was 11% (range, 1 to 45%). The 10-year overall survival rate was 78%. On univariate analysis, tumor size > or = 10 cm, high cellularity, presence of anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power fields, Ki-67 > or = 10%, and Ki-67 "hot spot" > or = 25% were associated with decreased metastasis-free or overall survival. Ploidy status was not associated with any adverse outcome.

The presence of any of these adverse prognostic factors can indicate the possibility of a more aggressive behavior in extraskeletal myxoid chondrosarcoma, and a closer follow-up is suggested.

Extraskeletal myxoid chondrosarcoma.

McGrory JE, Rock MG, Nascimento AG, Oliveira AM.

Mayo Clinic/Mayo Foundation, Rochester, MN, USA.

Clin Orthop 2001 Jan;(382):185-90 Abstract quote

The medical records and histologic material of 16 patients with extraskeletal myxoid chondrosarcoma were reviewed.

The mean age of the patients was 52 years. Thirteen tumors arose in the lower extremity. Thirteen patients presented with primary, localized disease, whereas three presented with pulmonary metastases. Treatment of the primary site included wide excision or amputation in 13 patients and marginal or intralesional resections with radiation in three patients. The mean followup was 7.4 years. Five patients were continuously disease free (5- and 10-year event free survival 43% and 14%, respectively).

Local recurrence developed in four, and metastases developed in six of 13 patients presenting with localized disease. Of six patients who received chemotherapy for systemic disease, four had disease progression and died, and two had a response to chemotherapy (one partial, one complete). The mean survival after onset of metastases was 45 months.

Overall 5- and 10-year survival was 87% and 63%, respectively.

The current series suggests that extraskeletal myxoid chondrosarcoma is an intermediate-grade neoplasm with a tendency toward recurrence and metastasis. Survival after relapse may be prolonged. More effective therapy for systemic disease is needed.

RECURRENCE Local recurrence in about 50% of cases with multiple recurrences common

METASTASIS
Am J Surg Pathol 1999 Jun;23(6):636-50

Metastases occurred in 35 (46%) of 76 patients

Lungs, bones

Extraskeletal myxoid chondrosarcoma with multiple skeletal metastases.

Takeda A, Tsuchiya H, Mori Y, Nonomura A, Tomita K.

Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Japan

J Orthop Sci 2000;5(2):171-4 Abstract quote

Pulmonary metastases are not unusual in extraskeletal myxoid chondrosarcoma; however, only two patients have been reported with multiple bony metastases.

We report here one patient with extraskeletal myxoid chondrosarcoma associated with lung and multiple bony metastases. After chemotherapy, the primary lesion was resected, but lung and multiple bony metastases were found 20 months later. The bony metastases were in the right femur, right humerus, and at multiple vertebral levels. Because of a pathologic fracture of the right femur, the metastases in the right femur and right humerus were surgically stabilized.

After chemotherapy, the lung metastases were resected, and those in the vertebral bodies were treated with radiotherapy.

TREATMENT Surgical resection
Chemotherapy
Radiotherapy

GENERAL

Extraskeletal myxoid chondrosarcoma. Long-term experience with chemotherapy.

Patel SR, Burgess MA, Papadopoulos NE, Linke KA, Benjamin RS.

Department of Melanoma/Sarcoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston.

Am J Clin Oncol 1995 Apr;18(2):161-3 Abstract quote

Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade soft tissue sarcoma that has been reported to have an indolent nature history, and relatively good prognosis. The majority of primary tumors are located in the extremities and they tend to be bulky at presentation. Studies with long-term follow-up have revealed the development of distant metastases in virtually all patients, eventually resulting in death.

We reviewed our experience with EMC over the last three decades.

The patient population was identified through a search of the database maintained by the Departments of Patient Studies, Pathology, and Melanoma-Sarcoma Medical Oncology. Eleven patients with histologically confirmed diagnosis of EMC were identified. The median age was 59 (37-81 years), and there were nine males and two females. Nine patients had an extremity location and the remaining two had a chest wall and abdominal wall primary, respectively. The median size of the primary tumor was 10 cm (range: 4-17 cm) in maximum dimension.

Ten of the eleven patients received chemotherapy, mainly with doxorubicin- and dacarbazine-based regimens. One patient is currently on beta-interferon. No objective responses were noted, to a median of 4 (2-6) cycles of chemotherapy. Three patients were treated with ifosfamide as a second-line chemotherapy without any benefit. Three patients have expired, two patients are alive with no evidence of disease, and six patients are alive with disease. The median follow-up is 5 years (range: 1.33-17 years) from diagnosis.

Although small numbers preclude adequate assessment, there is no evidence of efficacy of standard soft-tissue sarcoma chemotherapy in patients with EMC.

INTERFERON ALFA

Metastatic extraskeletal myxoid chondrosarcoma. Successful therapy with interferon alfa-2b.

Rubinger M, Plenderleith IH, Lertzman M, Worth AJ.

Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.

Chest 1995 Jul;108(1):281-2 Abstract quote

A patient with pulmonary metastatic extraskeletal myxoid chondrosarcoma (EMC), of unknown cause, responded dramatically to 16 months of therapy with interferon alfa-2b.

This is the first report of a significant response of a patient with EMC to this novel treatment approach.

Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Chondrosarcoma

Soft Tissue Tumors

Last Updated 7/31/2002

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PATHOGENESIS	CHARACTERIZATION
CHROMOSOMAL ABNORMALITIES
Extraskeletal Myxoid Chondrosarcoma With Neuroendocrine Differentiation A Pathologic, Cytogenetic, and Molecular Study of a Case With a Novel Translocation t(9;17)(q22;q11.2) M. Harris, M.D.; J. Coyne, F.R.C.Path; M. Tariq, B.Sc.; B. P. Eyden, Ph.D.; M. Atkinson, F.R.C.Path; A. J. Freemont, M.D.; J. Varley, Ph.D.; C. Attwooll, B.Sc.; N. Telford, B.Sc. From the Departments of Histopathology (M.H., B.P.E.), and Oncology Cytogenetics (M.T., N.T.), Christie Hospital, Manchester; the Department of Histopathology (J.C.), Withington Hospital, Manchester; the Department of Histopathology, Royal Oldham Hospital (M.A.); the Department of Osteo-articular Pathology, University of Manchester (A.J.F.); and the C.R.C. Department of Cancer Genetics (J.V., C.A.), Paterson Institute for Cancer Research, Manchester, U.K.	Am J Surg Pathol 2000;24:1020-1026 Abstract quote A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was histochemical, immunohistochemical, and ultrastructural evidence of neuroendocrine differentiation is reported. Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.
Translocation der(13;21)(q10;q10) in Skeletal and Extraskeletal Mesenchymal Chondrosarcoma. Naumann S, Krallman PA, Unni KK, Fidler ME, Neff JR, Bridge JA. Departments of Pathology and Microbiology (SN, PK, JRN, JAB), Orthopaedic Surgery (JRN, JAB), and Pediatrics (JAB), University of Nebraska Medical Center, Omaha, Nebraska.	Mod Pathol 2002 May;15(5):572-6 Abstract quote 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.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Radiographs
CT scan and MRI
Extraskeletal mesenchymal chondrosarcoma. Shapeero LG, Vanel D, Couanet D, Contesso G, Ackerman LV. Department of Radiology, Institut Gustave-Roussy, Villejuif, France. .	Radiology 1993 Mar;186(3):819-26 Abstract quote Among seven patients with extraskeletal mesenchymal chondrosarcoma (EMC), three children (aged 3-6 years) developed EMC in a central location and four adults (aged 38-54 years) developed EMC in both central and peripheral sites. Conventional radiography and tomography and computed tomography (CT) depicted EMC as a soft-tissue mass with ring, arc, stippled, and highly opaque calcifications in four patients. Contrast-enhanced CT showed lobulation and peripheral tumoral enhancement, sometimes with central low-attenuation areas. On magnetic resonance (MR) images, EMC was a lobulated mass with high signal intensity on T2-weighted images and enhancement with low-signal-intensity focal areas on contrast-enhanced T1-weighted images. All adults developed recurrences and/or metastases and died. Of the three children, two were living and free of disease at the end of the study and the third child died of chemotherapeutic-induced leukemia. Although imaging features of EMC are nonspecific, its chondroid-type calcifications and foci of low signal intensity within enhancing lobules may reflect its dual histopathologic morphologic characteristics of differentiated cartilage islands interspersed within vascular undifferentiated mesenchyme.
MRI of mesenchymal chondrosarcoma of the orbit: case report and review of the literature. Shinaver CN, Mafee MF, Choi KH. Department of Radiology, University of Illinois at Chicago Medical Center 60612, USA.	Neuroradiology 1997 Apr;39(4):296-301 Abstract quote Extraskeletal mesenchymal chondrosarcoma is a relatively uncommon entity, an orbital location being extremely rare. A review of the literature revealed 16 reported cases of primary orbital mesenchymal chondrosarcoma demonstrated by plain film and CT. To the best of our knowledge, the MRI features of orbital extraskeletal mesenchymal chondrosarcoma have not been previously reported. We present the case of an 18-year-old man with a 2-year history of progressive proptosis of the right eye who underwent CT, dynamic CT, MRI without and with gadolinium enhancement, and magnetic resonance angiography of the orbits. CT of orbital mesenchymal chondrosarcoma demonstrates a well-defined mass with multiple areas of fine and coarse calcification and shows moderate contrast enhancement. The noncalcified portions of the mass demonstrate signal intensity lower than or equal to gray matter on T1-weighted images and are isointense to the gray matter on T2-weighted images. Dynamic CT reveals delayed contrast enhancement. MRI has proven to be a valuable diagnostic tool in the diagnosis and differentiation of well-defined intraorbital masses. By a combination of CT and MRI, it appears mesenchymal chondrosarcoma can be differentiated from other intraorbital lesions, such as cavernous hemangioma, hemangiopericytoma, orbital amyloidosis and fibrous histiocytoma.
Nuclear Medicine
Radionuclide imaging in extraskeletal myxoid chondrosarcoma. Lin WY, Wang SJ, Yeh SH. Department of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan.	Clin Nucl Med 1995 Jun;20(6):524-7 Abstract quote The authors present a case of extraskeletal myxoid chondrosarcoma. The MR study clearly showed the extent of the tumor and a "rings and arcs" pattern appeared after Gadolinium-DTPA administration in the T1 weighted images. Dynamic Tc-99m MDP and Tc-99m DTPA scintigraphy showed increased blood flow in the mass. The delayed 3-hour images demonstrated moderate Tc-99m MDP uptake, but intense Tc-99m DTPA accumulation in the tumor. Surprisingly, the Ga-67 scan failed to demonstrate the tumor.
Laboratory Markers

HISTOLOGICAL TYPES	CHARACTERIZATION
General
Extraskeletal myxoid chondrosarcoma: a reappraisal of its morphologic spectrum and prognostic factors based on 117 cases. Meis-Kindblom JM, Bergh P, Gunterberg B, Kindblom LG. Gothenburg Musculoskeletal Tumor Center, Sahlgren University Hospital, Department of Pathology, Gothenburg University, Sweden.	Am J Surg Pathol 1999 Jun;23(6):636-50 Abstract quote Extraskeletal myxoid chondrosarcoma (EMC), a phenotypically and genotypically distinctive entity, has generally been viewed as a low-grade sarcoma. No studies regarding clinical and morphologic prognostic factors have been performed on a large series of cases with long-term follow-up because of the rarity and protracted clinical course of EMC. The clinical, morphologic, and immunohistochemical features of 117 previously unreported cases were studied and statistically analyzed. The male-to-female ratio was 2:1. The median patient age was 52 years (range, 6-89 years), and the median tumor size was 7 cm (range, 1.1-25 cm). All tumors occurred within the deep subcutis or deeper soft tissues, with 80% occurring in the proximal extremities or limb girdles and 20% in the trunk. Most initial tumor excisions were intralesional or marginal. Follow-up information was available in 99 cases (median, 9 years: range, 2 months-22 years). Forty-eight patients were disease-free, and 41 patients had evidence of disease (18 of these had died of disease). Ten additional patients survived, but their disease status was unknown. There were local recurrences in 40 (48%) of 83 patients, 23 (58%) of whom had multiple local recurrences. Metastases occurred in 35 (46%) of 76 patients. The estimated 5-, 10-, and 15-year survival rates were 90%, 70%, and 60%, respectively. All cases had histologic features characteristic of classical EMC, at least focally. Cellular foci devoid of myxoid matrix and reminiscent of chondroblastoma, Ewing's sarcoma, monophasic and poorly differentiated synovial sarcoma, fibrosarcoma, and rhabdoid tumor were identified in 29% cases. Older patient age, larger tumor size, and tumor location in the proximal extremity or limb girdle were adverse prognostic factors identified by multivariate analysis. Metastasis also adversely affected survival, although local recurrence did not. This study shows that EMC has a unique clinical course, including a high rate of local recurrence, prolonged survival after metastasis in some cases, and eventually a high rate of death due to tumor. These features distinguish EMC from low-grade sarcomas. This study shows that histologic grading is of no prognostic value in EMC because prognosis is dictated primarily by certain clinical features. Histologic recognition of classical EMC and cellular and solid, nonmyxoid variants is important, however, in view of EMC's distinctive biologic behavior.
Extraskeletal myxoid chondrosarcoma: A clinicopathologic, immunohistochemical, and molecular analysis of 18 cases Sumika Okamoto, MD Masanori Hisaoka, MD Tsuyoshi Ishida, MD Tetsuo Imamura, MD, etal	Hum Pathol 32:1116-1124. Abstract quote Extraskeletal myxoid chondrosarcoma (EMCS) is an uncommon clinicopathologically well-defined tumor, but its pathogenesis and biologic behavior are poorly understood. We reviewed 18 cases of EMCS to verify clinicopathologic features and immunohistochemical profiles together with molecular detection of the tumor-specific fusion genes. The tumors were located mainly in the proximal extremities and limb girdles (72%). Two tumors arose at unusual anatomic sites: the finger and the hip joint. Nine of the 17 followed-up patients were alive and disease free, 4 were alive with recurrences and/or metastases, and 4 died of the tumor. Fifteen tumors showed typical features of EMCS, and 3 had hypercellular areas in addition to conventional EMCS areas. The tumors were variably immunoreactive for S-100 protein (50%), NSE (89%), peripherin (60%), and synaptophysin (22%). Chromogranin A and some epithelial markers (AE1/AE3, CAM5.2, and epithelial membrane antigen) were entirely negative. Frequent expressions of the neural/neuroendocrine markers suggest possible neural/neuroendocrine differentiation in at least some EMCSs, in addition to chondroid differentiation. In a reverse-transcription polymerase chain reaction (RT-PCR) assay using paraffin-embedded specimens, EWS-CHN or TAF2N-CHN fusion gene transcripts characteristic of EMCS could be detected in 15 (83%) of the 18 cases: EWS-CHN type 1 in 11 cases, EWS-CHN type 2 in 1, and TAF2N-CHN in 3. Three fusion-negative cases included 2 conventional EMCSs and 1 considered a �cellular� variant of the tumor. None of 30 other soft tissue and bone tumors with myxoid or chondroid morphology that we examined contained these fusion genes. Thus, RT-PCR detection of EWS-CHN or TAF2N-CHN fusion gene using archival paraffin-embedded tissue is a feasible and useful ancillary technique for the diagnosis of EMCS.
VARIANTS
RHABDOID FEATURES
Extraskeletal Myxoid Chondrosarcoma with Rhabdoid Features, with Special Reference to Its Aggressive Behavior. Oshiro Y, Shiratsuchi H, Tamiya S, Oda Y, Toyoshima S, Tsuneyoshi M. Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University.	Int J Surg Pathol 2000 Apr;8(2):145-152 Abstract quote The presence of rhabdoid cells has been reported in various types of malignant neoplasms. Thirty-six cases of extraskeletal myxoid chondrosarcoma (EMC) were reviewed, and three of them revealed rhabdoid features. These cases contained cells having prominent eosinophilic globular cytoplasm, but were otherwise typical of EMC. Immunohistochemically, cytokeratin (CAM 5.2) was positive in three of 20 cases (15%), including two of the three with rhabdoid features. The rhabdoid cells were also immunostained with vimentin. The 5-year survival rate in the 26 cases with follow-up information was 73%, and the 10-year survival rate was 63%. The cases with rhabdoid features had a significantly poorer prognosis (p=0.0271). This study suggests that presence of rhabdoid features is a predictor of aggressive behavior in EMC, as it was shown to be in other mesenchymal neoplasms.
HIGH GRADE HISTOLOGY
High-grade extraskeletal myxoid chondrosarcoma: a high-grade epithelioid malignancy. Lucas DR, Fletcher CD, Adsay NV, Zalupski MM. Department of Pathology, Wayne State University School of Medicine, Harper Hopspital and Karmanos Cancer Center, Detroit, MI, USA.	Histopathology 1999 Sep;35(3):201-8 Abstract quote AIMS: Extraskeletal myxoid chondrosarcoma is typically a low-to-intermediate grade sarcoma that is associated with a prolonged clinical course. High-grade forms are rare and not well characterized. In this series we report the clinicopathological, immunohistochemical and ultrastructural findings in four cases of high-grade extraskeletal myxoid chondrosarcoma. METHODS AND RESULTS: The patients were three men and one woman (ages 34-73 years) with tumours located in the thigh (two cases), paraspinal soft tissue and perineum. Three patients had metastases, one at 12 weeks, one at 10 months, and one at presentation of recurrent tumour. In the latter case the original tumour was low grade and became high grade when it recurred 3.5 years later. All three patients died of disease. One patient was lost to follow-up. The most striking histological feature in all four tumours was the presence of numerous large epithelioid cells. These cells were arranged in cords within myxoid matrix and in sheets devoid of matrix. Two tumours had areas of conventional extraskeletal myxoid chondrosarcoma intermixed with the high-grade areas. One tumour showed transition to high-grade spindle cell sarcoma. One tumour had cells with rhabdoid features. Immunohistochemically, two tumours focally expressed S100 protein, and one focally expressed EMA. All were negative with cytokeratin, desmin, smooth muscle actin, HMB45, CD31 and CD34. Ultrastructural features in three cases were compatible with chondrosarcoma; one tumour had aggregates of microtubules within rough endoplasmic reticulum, a characteristic feature of this tumour. CONCLUSIONS: High-grade extraskeletal myxoid chondrosaroma is a rare and aggressive soft tissue sarcoma, and should be included in the differential diagnosis of other epithelioid malignancies.

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
IMMUNOPEROXIDASE	S100+ EMA+/-
ELECTRON MICROSCOPY
An ultrastructural study of extraskeletal mesenchymal chondrosarcoma. Sato N, Minase T, Yoshida Y, Narimatsu E, Muroya K, Asaishi K, Kikuchi K.	Acta Pathol Jpn 1984 Nov;34(6):1355-63 Abstract quote A rare case of extraskeletal mesenchymal chondrosarcoma in a 47-year-old woman is reported. The tumor was located in the soft tissue of left upper arm without any involvement of the humerus. The outer portion of the tumor was histologically composed of primitive mesenchymal cells, and the inner portion showed zones of cartilaginous differentiation. Ultrastructurally, the tumor cells in the primitive areas had a relatively small number of mitochondria, rough endoplasmic reticulum, and free polysomes, and the matrix of the tumor consisted of dense bundles of collagen fibrils. The cartilaginous cells seen in the central portion of tumor were embedded in the matrix of abundant collagen fibrils and matrix granules. They had polysomes, well-developed Golgi complexes, and ample rough endoplasmic reticulum frequently with dilatation. Clear zones adjacent to the cells were seen in the extracellular matrix. With a review of the literature, the histogenesis of this particular tumor is discussed.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Extraskeletal myxoid chondrosarcoma. A clinicopathologic study of ten patients with long-term follow-up. Saleh G, Evans HL, Ro JY, Ayala AG. Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030.	Cancer 1992 Dec 15;70(12):2827-30 Abstract quote Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma that has been reported to have a relatively good prognosis. The authors report ten patients with EMC on whom there was a minimum follow-up of 10 years. The patients' ages ranged from 31 to 72 years (mean, 57 years); there were six men and four women (seven white, three black). The tumor locations included the knee area and thigh (three patients each), the shoulder (two patients), and the leg and foot (one patient each). The tumors ranged from 3.5 to 18 cm in greatest dimension (median, 11.5 cm). All cases had typical histologic features. Lung metastases developed in all patients but one, and three patients had extrathoracic metastases (one in regional lymph nodes; one in subcutis; and one widespread). Four of the patients who had metastases also had local recurrence, as did the only patient without known metastases. Seven patients died of tumor at 4, 5, 8, 10, 15, 16, and 17 years, respectively, and the three remaining patients were alive with metastatic disease at latest follow-up of 13, 14, and 16 years. The authors' results are distinctly different from those previously reported in series with shorter follow-up times. The authors conclude that extraskeletal myxoid chondrosarcomas are indolent but resilient and capricious tumors with a high potential for metastasis, especially to the lungs, over the long-term.
	Am J Surg Pathol 1999 Jun;23(6):636-50 Estimated 5-, 10-, and 15-year survival rates were 90%, 70%, and 60%, respectively.
Extraskeletal myxoid chondrosarcoma: a clinicopathologic, immunohistochemical, and ploidy analysis of 23 cases. Oliveira AM, Sebo TJ, McGrory JE, Gaffey TA, Rock MG, Nascimento AG. Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA	Mod Pathol 2000 Aug;13(8):900-8 Abstract quote Twenty-three cases of extraskeletal myxoid chondrosarcoma, evaluated at the Mayo Clinic between 1968 and 1996, were studied for clinicopathologic features, immunohistochemical profile, Ki-67 activity, and ploidy status to identify adverse prognostic factors. Females and males were equally affected, and the median age at diagnosis was 50 years. The tumors were located mainly in the lower extremities (83%), and the median tumor size was 9.5 cm. Sixteen tumors showed low cellularity (70%), and eight tumors had high mitotic activity (more than two per 10 high-power fields). The tumors were immunoreactive for vimentin (89%), synaptophysin (72%), epithelial membrane antigen (28%), and S-100 protein (17%). Nine tumors were diploid, three aneuploid, and one tetraploid. Mean Ki-67 activity was 11% (range, 1 to 45%). The 10-year overall survival rate was 78%. On univariate analysis, tumor size > or = 10 cm, high cellularity, presence of anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power fields, Ki-67 > or = 10%, and Ki-67 "hot spot" > or = 25% were associated with decreased metastasis-free or overall survival. Ploidy status was not associated with any adverse outcome. The presence of any of these adverse prognostic factors can indicate the possibility of a more aggressive behavior in extraskeletal myxoid chondrosarcoma, and a closer follow-up is suggested.
Extraskeletal myxoid chondrosarcoma. McGrory JE, Rock MG, Nascimento AG, Oliveira AM. Mayo Clinic/Mayo Foundation, Rochester, MN, USA.	Clin Orthop 2001 Jan;(382):185-90 Abstract quote The medical records and histologic material of 16 patients with extraskeletal myxoid chondrosarcoma were reviewed. The mean age of the patients was 52 years. Thirteen tumors arose in the lower extremity. Thirteen patients presented with primary, localized disease, whereas three presented with pulmonary metastases. Treatment of the primary site included wide excision or amputation in 13 patients and marginal or intralesional resections with radiation in three patients. The mean followup was 7.4 years. Five patients were continuously disease free (5- and 10-year event free survival 43% and 14%, respectively). Local recurrence developed in four, and metastases developed in six of 13 patients presenting with localized disease. Of six patients who received chemotherapy for systemic disease, four had disease progression and died, and two had a response to chemotherapy (one partial, one complete). The mean survival after onset of metastases was 45 months. Overall 5- and 10-year survival was 87% and 63%, respectively. The current series suggests that extraskeletal myxoid chondrosarcoma is an intermediate-grade neoplasm with a tendency toward recurrence and metastasis. Survival after relapse may be prolonged. More effective therapy for systemic disease is needed.
RECURRENCE	Local recurrence in about 50% of cases with multiple recurrences common
METASTASIS	Am J Surg Pathol 1999 Jun;23(6):636-50 Metastases occurred in 35 (46%) of 76 patients Lungs, bones
Extraskeletal myxoid chondrosarcoma with multiple skeletal metastases. Takeda A, Tsuchiya H, Mori Y, Nonomura A, Tomita K. Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Japan	J Orthop Sci 2000;5(2):171-4 Abstract quote Pulmonary metastases are not unusual in extraskeletal myxoid chondrosarcoma; however, only two patients have been reported with multiple bony metastases. We report here one patient with extraskeletal myxoid chondrosarcoma associated with lung and multiple bony metastases. After chemotherapy, the primary lesion was resected, but lung and multiple bony metastases were found 20 months later. The bony metastases were in the right femur, right humerus, and at multiple vertebral levels. Because of a pathologic fracture of the right femur, the metastases in the right femur and right humerus were surgically stabilized. After chemotherapy, the lung metastases were resected, and those in the vertebral bodies were treated with radiotherapy.
TREATMENT	Surgical resection Chemotherapy Radiotherapy
GENERAL
Extraskeletal myxoid chondrosarcoma. Long-term experience with chemotherapy. Patel SR, Burgess MA, Papadopoulos NE, Linke KA, Benjamin RS. Department of Melanoma/Sarcoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston.	Am J Clin Oncol 1995 Apr;18(2):161-3 Abstract quote Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade soft tissue sarcoma that has been reported to have an indolent nature history, and relatively good prognosis. The majority of primary tumors are located in the extremities and they tend to be bulky at presentation. Studies with long-term follow-up have revealed the development of distant metastases in virtually all patients, eventually resulting in death. We reviewed our experience with EMC over the last three decades. The patient population was identified through a search of the database maintained by the Departments of Patient Studies, Pathology, and Melanoma-Sarcoma Medical Oncology. Eleven patients with histologically confirmed diagnosis of EMC were identified. The median age was 59 (37-81 years), and there were nine males and two females. Nine patients had an extremity location and the remaining two had a chest wall and abdominal wall primary, respectively. The median size of the primary tumor was 10 cm (range: 4-17 cm) in maximum dimension. Ten of the eleven patients received chemotherapy, mainly with doxorubicin- and dacarbazine-based regimens. One patient is currently on beta-interferon. No objective responses were noted, to a median of 4 (2-6) cycles of chemotherapy. Three patients were treated with ifosfamide as a second-line chemotherapy without any benefit. Three patients have expired, two patients are alive with no evidence of disease, and six patients are alive with disease. The median follow-up is 5 years (range: 1.33-17 years) from diagnosis. Although small numbers preclude adequate assessment, there is no evidence of efficacy of standard soft-tissue sarcoma chemotherapy in patients with EMC.
INTERFERON ALFA
Metastatic extraskeletal myxoid chondrosarcoma. Successful therapy with interferon alfa-2b. Rubinger M, Plenderleith IH, Lertzman M, Worth AJ. Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.	Chest 1995 Jul;108(1):281-2 Abstract quote A patient with pulmonary metastatic extraskeletal myxoid chondrosarcoma (EMC), of unknown cause, responded dramatically to 16 months of therapy with interferon alfa-2b. This is the first report of a significant response of a patient with EMC to this novel treatment approach.

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE	Rare
AGE RANGE-MEDIAN	Mean 52 years
SEX (M:F)	2:1

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Chondroblastoma
Ewing's sarcoma
Fibrosarcoma
Hemangiopericytoma
Malignant hemangiopericytoma and other sarcomas with hemangiopericytoma-like pattern. Tsuneyoshi M, Daimaru Y, Enjoji M.	Pathol Res Pract 1984 May;178(5):446-53 Abstract quote This clinicopathologic study concerns 19 cases of malignant hemangiopericytoma among 755 cases of soft tissue sarcomas. The age of the patients ranged from 18 to 76 years, with a median of 43 years. Tumors occurred on the trunk in 8, lower extremities in 5, the head in 3, and the retroperitoneum in 3. According to follow-up information, nine of the 19 patients had died. Histologically the tumor was characterized by its homogeneous vascular pattern, its uniform cell population and a wide range of cellular anaplasia. After extensive sampling of the tumors, a comparative light microscopy revealed differences in diagnostic histology between malignant hemangiopericytoma and other soft tissue sarcomas with a hemangiopericytoma-like vascular pattern. The frequency of appearance of such pericytoma pattern in different soft tissue sarcomas was as follows: 4/4 cases (100%) in extraskeletal mesenchymal chondrosarcoma, 11/14 (79%) in infantile fibrosarcoma, 27/45 (60%) in synovial sarcoma, 62/201 (30%) in malignant fibrous histiocytoma, 9/37 (25%) in malignant schwannoma and 6/72 (8%) in liposarcoma.
Rhabdoid tumor
Synovial sarcoma