Intriguing Case
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Chordomalike Soft Tissue Sarcoma in the Leg: A Light and Electron Microscopic and Immunohistochemical Study Markku Miettinen, MD, Francis H. Gannon, MD, and Richard Lackman, MD Departments of Pathology and Cell Biology and Orthopedic Surgery, Thomas Jefferson Uwiversity, 11I South 11th Street, Philadelphia, Pennsylvania 19107, USA
A soft tissue tumor in the leg of a 67-year-old woman is described. This large tumor below the knee area infiltrated extensively the deep and superficial soft tissues but did not involve the bones. The tumor cells formed nodules resembling the architecture seen in chondroid tumors and chordoma. The tumor cells were often vacuolized, and there was extracellular myxoid matrix similar t o that in chordoma or myxoid chondrosarcoma. Immunohistochemistry showed keratins 8 and 19, epithelial membrane antigen, and vimentin in most tumor cells, and there was also S-100 protein positivity in a number of tumor cells. Electron microscopy showed desmosomelike cell junctions and bundles of intermediate filaments resembling those seen in many epithelial neoplasms. Thus the tumar resernbled chordoma in many respects. Because clinically no other primary tumor was found, this tumor is probably a chordomalike primary soft tissue sarcoma different from typical extraskeletal rnyxoid chondrosarcoma or chordoid sarcoma.
KEY WORDS: chordorna, electron microscopy, immunohistochemistry, sarcoma, soft tissue.
INTRODUCTION Chordoma is a bone tumor typical of the axial skeleton. Most commonly it occurs in the sacrococcygeal area or in other portions of the vertebral column.’ Besides this, it can present extraosseously in the skull base, presumably originating from the notochordal rests of this location. Chordomas are not seen as primary peripheral soft tissue tumors, although they may recur or metastasize in such locations. Two tumor entities with certain resemblances t o chordoma occur in peripheral soft tissues, in-
cluding the extremities: the so-called parachordoma’ and the extraskeletal myxoid chondrosarcoma (ESMC),3*4some forms of which are called chordoid sarcoma. We report a soft tissue sarcoma from the lower extremity that had a resemblance t o chordoma rather than chondrosarcoma by immunohistochemistry and electron microscopy. The nature and taxonomic position of this tumor are discussed.
CLINICAL HISTORY A 6 7-year-old woman had experienced left knee pain for 1 years. Initial medical treatment for arthritis gave only mini-
’/.
Address corremondence to
M.Miettinen
Ultrastructural Pathology, 16:577-586, 1992 Copyright
0 1992 by Hemisphere Publishing Corporation
577
M. Miettinen et a1
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578 ma1 relief. Imaging studies and arthroscopy showed a meniscal tear and a popliteal cyst. Later a knee arthroplasty was performed, and biopsy upon this procedure revealed tumor, which was diagnosed as chondrosarcoma. The patient had knee contracture and was unable to use her left leg. Given the extensive distribution of this tumor and involvement of the neurovascular bundles, no limb salvage approach was possible, and above the knee amputation was performed. Although chest radiographs were normal at the time of surgery, multiple pulmonary metastases developed during the following months, and the patient died 1 1 months after presentation. No autopsy was performed.
MATERIALS AND METHODS For light microscopy, widely sampled tumor tissue was fixed in 4% buffered formaldehyde and embedded in paraffin. For electron microscopy, small pieces of formaldehyde-fixed tumor tissue were sequentially postfixed in 2.5% phosphatebuffered glutaraldehyde and 1.O% osmium tetroxide and were embedded in Araldite. Representative thin sections ( 1 p m ) stained with toluidine blue were studied from selected areas. lmmunohistochemistry was done by the avidin-biotin-peroxidase method w i t h diaminobenzine supplemented by 0.02% hydrogen peroxide used as the chromogen. The primary antibodies employed in this study are listed in the table. Protease digestion (0.05% pepsin in HCI, pH 1.8 t o
2.0, for 30 minutes) was performed before cytokeratin immunostaining. Appropriate negative and positive controls were run.
GROSS PATHOLOGY The above the knee amputation specimen showed a widespread tumor involving the soft tissues of the knee area but sparing the bones. The tumor also infiltrated the knee joint (Fig. 1). There were tumor masses surrounding the knee on the popliteal aspect and growing between tibia and fibula. The largest tumor nodule was located posteriorly and measured l l x 5 x 5 cm. The ventral surface of the knee also contained an 8.5 x 3 x 2 cm tumor nodule approaching the skin. There were several smaller superficial tumor nodules located subcutaneously. There was n o tumor involvement of the bones or skin. On cut surface, the tumor tissue was grayish yellow, glistening, and soft. Some nodularity and small necroses were visible.
LIGHT MICROSCOPY The tumor was composed of cellular nodules separated b y thick fibrous septa. Some of the nodules showed nests of metaplastic, benign-appearing bone in their periphery (Fig. 2). The cellular nodules contained medium-sized cells with moderately sized, relatively uniform nuclei. The cells were mostly polygonal and had abundant, variably eosinophilic, sometimes vacuolated cytoplasm. There was typically loose myxoid matrix between the tumor cells (Fig. 3). In some areas, the tu-
TABLE Antibodies Used in the Study Antibody
Dilution
Source
C A M 5.2 (specific for keratin 8) Keratin 1 9
1 : 10 1:50 1: 4 0 1:lO 1 : 12,800 1 : 100 1 :800 1 : 3,200 1:50
Beckton-Dickinson, Mountain View, CA Dakopatts, Carpinteria, CA Dakopatts Dakopatts Enzo Biochem, New York, NY Dakopatts Dakopatts Enzo Dakopatts
Epithelial membrane antigen Vimentin Muscle-specific actin IHHF-35) Oesmin (monoclonal D-33) S-100 protein (polyclonal) Melanoma-specific antigen (HMB-45) Factor VIII-related antigen
Intriguing Case: Chordomalike Soft Tissue Sarcoma
579
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closely apposed without significant cellular projections. In many cells, large vacuoles and multiple lipid droplets were present. Arrays of intermediate filaments were often seen, and some of these formed tonofilamentlike bundles. Glycogen particles often formed rosettelike groups (Fig. 6). Some cells were joined by desmosomelike cell-to-cell junctions (Fig. 7).
IMMUNOHISTOCHEMISTRY
FIG. 1 The tumor involves extensively the soft tissues around the knee, predominantly growing in the popliteal aspect. The proximal tibia is seen below and the femur above, 100% reduction. mor cells were spindle shaped but still relatively uniform (Fig. 4). Approximately 1 2 mitoses were seen per 10 high-power fields. Scattered lymphocytic infiltration was seen within the cellular nodules. Necrotic foci and hyalinized areas were commonly seen within the cellular nodules.
ELECTRON MICROSCOPY The tumor cells were oval t o polygonal and had moderately sized nuclei with a vesicular appearance and marginated chromatin. The cytoplasm was abundant with welldeveloped rough endoplasmic reticulum and multiple polyribosomes. Abundant collagen fibers were seen between tumor cells in some areas. Thus a significant number of tumor cells had fibroblastlike characteristics (Fig. 5). The cells in the central aspects of cellular nests were
A major proportion of tumor cells were cytokeratin-positive with CAM 5.2 antibody specific for keratin 8 (Fig. 8a). Keratin 1 9 immunostaining showed similar extensive positivity within the cellular nodules of the tumor, as did AEI antibody, which also reacts with keratin 19. AE8 antibody specific for keratin 1 3 was negative. The majority of the tumor cells were also positive for epithelial membrane antigen. The tumor cells were uniformly positive for vimentin (Fig. 8b). Muscle actin and desmin were only seen in the vessel walls or muscle elements outside the tumor tissue (Fig. 8c). A significant proportion of tumor cells (about 30%) was positive for S-100 protein (Fig. 8d). The 5-100 protein-positive areas were not morphologically different from the rest of the areas. Staining for melanomaspecific antigen (HMB-45 antibody) was negative. lmmunostaining for factor Vlll labeled vascular endothelium but not the tumor cells.
DISCUSSION The present soft tissue tumor from the knee area has features that necessitate considering several tumor entities seen in soft tissue and bone. The differential diagnoses are especially chordoma, ESMC (chordoid sarcoma), and the so-called parachordoma. Also, the diagnoses of malignant mixed tumor of sweat glands and metastatic carcinoma may be considered on the basis of immunohistochemical findings. The present tumor resembles chordoma in several respects. By light microscopy, the tumor cells show epitheliallike clustering, cytoplasmic vacuolization, and
M. Miettinen et a1
Ultrastruct Pathol Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
580
FIG. 2
The tumor consists of cellular nodules separated b y fibrous septa. Metaplastic bone is seen in the center. Hematoxylin and eosin, x 50.
myxoid extracellular matrix within the cellular lobules. Ultrastructurally observed desmosomelike junctions and bundles of filaments are similar t o those described in ~ h o r d o m almmunohistochemically .~ identified keratin, epithelial membrane antigen, and vimentin immunoreactivity is typically seen in chordoma.6-8Furthermore, the tumor showed S-I00 protein immunostaining, as is seen in chordoma.’ The extraskeletal location in the leg differs from the usual site of true chordoma, however, which is a neoplasm of the axial skeleton typically seen in the sacral area.’ Metastatic chordoma may be seen in peripheral locations. We have seen metastatic chordoma in skin of lower extremity, buttocks and chest wall, but not in deep locations in the lower extremity. In the present case, there was no history or evidence of chordoma in any primary location. We hold that this tumor is a soft tissue sarcoma closely
resembling chordoma, although w e are unable t o provide a satisfactory explanation for its histogenesis. In 1977 Dabska’ described a series of chordomalike peripheral soft tissue tumors seen in the extremities and the trunk and named these tumors parachordomas, which she thought formed an entity. By the light microscopic illustrations in Dabska’s report, parachordoma seems t o be morphologically unique tumor, often containing a biphasic pattern with small primitive cells forming solid clusters and cartilaginous areas resembling the biphasic structure of mesenchymal chondrosarcoma. Even true glandular structures resembling embryonal epithelia may be seen.’ The present tumor did not contain such elements. It also seems that parachordomas are clinically of a low-grade malignant nature compared with our fatal chordomalike sarcoma. The literature on
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FIG. 3 The neoplastic cells are polygonal, vacuolated, and relatively uniform. Hematoxylin and eosin, x 220.
FIG. 4 Some nests of tumor cells have a spindle-cell appearance. Hematoxylin and eosin, x 220.
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582
FIG. 5 Electron microscopy shows fibroblastlike characteristics in a number of tumor cells, which show abundant rough endoplasmic reticulum and are separated by collagenous intercellular material, x 10,400. parachordoma since then has been scant, and no ultrastructural or immunohistochemical data are available to compare parachordoma with other entities. A tumor called chordoma periphericum and believed to represent parachordorn? was reported by Povysil and Matejovsky. This was a bone tumor that arose in the tibia; no further clinical details were available. This tumor had a lobular histologic pattern, and electron microscopy showed multiple cytoplasmic vacuoles and an abundance of glycogen, features that resemble those of chordoma. No immunohistochemical data were available. ESMC, some variants of which apparently have been called chordoid sarcoma, has architectural features somewhat similar t o those of the present tumor. Both electron microscopic and immunohistochemical features of ESMC, however, seem to be at variance with our chordoma-
like sarcoma. ESMC is more closely related to chondrosarcoma than chordoma as suggested by electron microscopy, where ESMC shows scalloped cellular outlines and a lack of true desmosomes,4~”~’3 similar t o the ultrastructure of chondrosarcoma.’4 Also, immunohistochemical comparison with chordoma shows that ESMC does not have keratin^,^,'^ although epithelial membrane antigen has been described in some cases.” A case of intraosseous chordoid sarcoma from the scapulat6 contained prominent cytoplasmic lipid droplets and was considered a possible brown fat tumor. In retrospect, however, the histologic illustrations suggest a relationship with ESMC. One case of chordoid sarcoma from soft tissues of the posterior neck reported by Tanaka and Asao17 illustrates histologic features suggestive of chordoma with trabeculae of epitheliallike tumor cells in myx-
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Intriguing Case: Chordomalike Soft Tissue Sarcoma
583
FIG. 6 Electron microscopy shows multiple lipid droplets and cytoplasmic intermediate filament bundles. Glycogen particles are also evident, x 10,400.
FIG. 7 Cell junctions are visible, some of which resemble desmosomes, x 34,200.
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584 M. Miettinen et a1
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Intriguing Case: Chordomalike Soft Tissue Sarcoma
oid matrix; electron microscopy described nonspecific features, and there was no mention about the presence or absence of desmosomes. No immunohistochemistry was available a t that time. The tumor was located extraosseously in the posterior neck, but because of its massive size it was close to the vertebral bones. Clear cell chondrosarcoma, although a bone tumor, can be considered in the differential diagnosis in the present case, but this tumor usually shows regular chondroid features as well and by electron microscopy has an unmistakable chondroid appearance with a scalloped outer membrane and cells floating in abundant loose matrix. Focusing on the prominent presence of epithelial markers, several other tumor types, especially synovial sarcoma, primary sweat gland carcinomas, and metastatic carcinomas, have to be considered in the differential diagnosis. Malignant mixed tumor (chondroid syringoma) arising in sweat glands of the skin can be theoretically considered in our case, but this was a massive deep soft tissue tumor with no apparent primary skin involvement (although subcutaneous nodules were present). Also, the present tumor did not have the glandular differentiation described in cutaneous malignant mixed tumors.” Finally, metastatic carcinoma, especially of renal origin, has t o be considered, although in our case the soft tissue tumor was clinically the primary disease manifestation with a long clinical duration. This and the lack of any clinical evidence of primary renal carcinoma make such a diagnosis most unlikely. 18r19
REFERENCES 1. Huvos A. Chordoma. In: Huvos A, ed. Bone Tumors. 2nd ed. Philadelphia: Saunders; 1991 : 599-624.
2. Dabska M. Parachordoma. A new clinicopathologic entity. Cancer. 1977;40:1586-1592. 3. Enzinger FM, Shiraki M. Extraskeletal myxoid chondrosarcoma. A n analysis of 34 cases. Hum Pathol. 1972:3:421-435. 4. Weiss SW. Ultrastructure of the so called “chordoid sarcoma.” Evidence supporting cartilaginous differentiation. Cancer. 1976;37:
300-306. 5. Erlandson RA, Tandler B, Lieberman PH, Higinbotham NL. Ultrastructure of human chordoma. Cancer Res. 1968;28:2115-2125. 6 Miettinen M, Lehto V-P, Dahl D, Virtanen I. Differential diagnosis of chordoma, chondroid and ependymal tumors as aided b y antiintermediate filament antibodies. A m J Pathol. 1983;1 12:160-169. 7 Abenoza P, Sibley RK. Chordoma: an immunohistologic study. Hum Pathol. 1986;17:744-
747. 8 Salisbury JR, lsaacson PG. Demonstration of cytokeratins and epithelial membrane antigen in chordomas and human fetal notochord. A m J Surg Pathol. 1985;9:791-797. 9 Nakamura Y, Becker LE, Marks A. 5100Protein in human chordoma and human and rabbit notochord. Arch Paihol lab Med. 1983;
107:l18-120. 10. Povysil C, Matejovsky Z. A comparative ultrastructural study of chondrosarcoma, chordoid sarcoma, chordoma and chordoma periphericum. Paihol Res Pract. 1985;179:546-559. 1 1 . Dardick I, Lgace R, Carlier MT, Jung RC. Chordoid sarcoma (extraskeletal myxoid chondrosarcoma). A light and electron microscope study. Virchows Arch Pathol Anat. 1983;399:
61-78. 12. Martin RF, Melnick PJ, Warner NE, Terry R, Bullock WK, Schwinn CP. Chordoid sarcoma. A m J Clin Pathol. 1973;59:623-635. 13. Pardo-Mindan FJ, Guillen FJ, Villas C, Vazquez JJ. A comparative ultrastructural study of chondrosarcoma, chordoid sarcoma, and chordoma. Cancer. 1981;47:2611-2619. 14. Erlandson RA, Huvos AG. Chondrosarcoma: a light and electron microscopic study. Cancer.
1974;34:1642-1652. 15. Wick MR, Burgess JH, Manivel JC. A reassessment of ”chordoid sarcoma.” Ultrastructural and immunohistochemical comparison w i t h chordoma and skeletal myxoid chondrosarcoma. M o d Pathol. 1988;1 :433-443. 16. Bender BL, Barnes L, Yunis EJ. lntraosseous “chordoid” sarcoma, chondroblastic or li-
_ _
FIG. 8 lmmunohistochemical profile of chordomalike soft tissue sarcoma. (a) The tumor cells are uniformly positive for keratin 8, x 320. (b) Both the tumor cells and the fibrous stroma are vimentin positive, x 320. (c) The tumor is negative for muscle actins, which are present in vessel walls, x 160. (d) The tumor cell nests show S- 100 protein immunostaining, x 320.
M. M i e t t i n e n et a1
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poblastic origin? Virchows Arch Pathol Anat Histol. 1980;387:241-249. 17. Tanaka N, Asao T. Chordoid sarcoma of the soft tissue of the nape of the neck: a case with a 20-year follow-up. Virchows Arch Pathol Anat Histol. 1978;379:261-268. 18. Le Charpentier Y, Forest M, Postel M, Torneno 6,Abelanet R. Clear-cell chondrosarcoma. A report of five cases including ultrastructural study. Cancer. 1979;44:622-629. 19. Angervall L, Kindblom L-G. Clear-cell chondro-
sarcoma. A light- and electron-microscopic and histochemical study of t w o cases. Virchows Arch Pathol Anat Histol. 1980;389:27-
41. 20. Redono C, Rocamora A, Villoria F, Garcia M. Malignant mixed tumor of the skin: malignant 1690chondroid syringoma. Cancer. 1990;49:
1696. Accepted in revised form October 3, 1997.
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Chordomalike Soft Tissue Sarcoma in the Leg: A Light and Electron Microscopic and Immunohistochemical Study Markku Miettinen, MD, Francis H. Gannon, MD, and Richard Lackman, MD Departments of Pathology and Cell Biology and Orthopedic Surgery, Thomas Jefferson Uwiversity, 11I South 11th Street, Philadelphia, Pennsylvania 19107, USA
A soft tissue tumor in the leg of a 67-year-old woman is described. This large tumor below the knee area infiltrated extensively the deep and superficial soft tissues but did not involve the bones. The tumor cells formed nodules resembling the architecture seen in chondroid tumors and chordoma. The tumor cells were often vacuolized, and there was extracellular myxoid matrix similar t o that in chordoma or myxoid chondrosarcoma. Immunohistochemistry showed keratins 8 and 19, epithelial membrane antigen, and vimentin in most tumor cells, and there was also S-100 protein positivity in a number of tumor cells. Electron microscopy showed desmosomelike cell junctions and bundles of intermediate filaments resembling those seen in many epithelial neoplasms. Thus the tumar resernbled chordoma in many respects. Because clinically no other primary tumor was found, this tumor is probably a chordomalike primary soft tissue sarcoma different from typical extraskeletal rnyxoid chondrosarcoma or chordoid sarcoma.
KEY WORDS: chordorna, electron microscopy, immunohistochemistry, sarcoma, soft tissue.
INTRODUCTION Chordoma is a bone tumor typical of the axial skeleton. Most commonly it occurs in the sacrococcygeal area or in other portions of the vertebral column.’ Besides this, it can present extraosseously in the skull base, presumably originating from the notochordal rests of this location. Chordomas are not seen as primary peripheral soft tissue tumors, although they may recur or metastasize in such locations. Two tumor entities with certain resemblances t o chordoma occur in peripheral soft tissues, in-
cluding the extremities: the so-called parachordoma’ and the extraskeletal myxoid chondrosarcoma (ESMC),3*4some forms of which are called chordoid sarcoma. We report a soft tissue sarcoma from the lower extremity that had a resemblance t o chordoma rather than chondrosarcoma by immunohistochemistry and electron microscopy. The nature and taxonomic position of this tumor are discussed.
CLINICAL HISTORY A 6 7-year-old woman had experienced left knee pain for 1 years. Initial medical treatment for arthritis gave only mini-
’/.
Address corremondence to
M.Miettinen
Ultrastructural Pathology, 16:577-586, 1992 Copyright
0 1992 by Hemisphere Publishing Corporation
577
M. Miettinen et a1
Ultrastruct Pathol Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
578 ma1 relief. Imaging studies and arthroscopy showed a meniscal tear and a popliteal cyst. Later a knee arthroplasty was performed, and biopsy upon this procedure revealed tumor, which was diagnosed as chondrosarcoma. The patient had knee contracture and was unable to use her left leg. Given the extensive distribution of this tumor and involvement of the neurovascular bundles, no limb salvage approach was possible, and above the knee amputation was performed. Although chest radiographs were normal at the time of surgery, multiple pulmonary metastases developed during the following months, and the patient died 1 1 months after presentation. No autopsy was performed.
MATERIALS AND METHODS For light microscopy, widely sampled tumor tissue was fixed in 4% buffered formaldehyde and embedded in paraffin. For electron microscopy, small pieces of formaldehyde-fixed tumor tissue were sequentially postfixed in 2.5% phosphatebuffered glutaraldehyde and 1.O% osmium tetroxide and were embedded in Araldite. Representative thin sections ( 1 p m ) stained with toluidine blue were studied from selected areas. lmmunohistochemistry was done by the avidin-biotin-peroxidase method w i t h diaminobenzine supplemented by 0.02% hydrogen peroxide used as the chromogen. The primary antibodies employed in this study are listed in the table. Protease digestion (0.05% pepsin in HCI, pH 1.8 t o
2.0, for 30 minutes) was performed before cytokeratin immunostaining. Appropriate negative and positive controls were run.
GROSS PATHOLOGY The above the knee amputation specimen showed a widespread tumor involving the soft tissues of the knee area but sparing the bones. The tumor also infiltrated the knee joint (Fig. 1). There were tumor masses surrounding the knee on the popliteal aspect and growing between tibia and fibula. The largest tumor nodule was located posteriorly and measured l l x 5 x 5 cm. The ventral surface of the knee also contained an 8.5 x 3 x 2 cm tumor nodule approaching the skin. There were several smaller superficial tumor nodules located subcutaneously. There was n o tumor involvement of the bones or skin. On cut surface, the tumor tissue was grayish yellow, glistening, and soft. Some nodularity and small necroses were visible.
LIGHT MICROSCOPY The tumor was composed of cellular nodules separated b y thick fibrous septa. Some of the nodules showed nests of metaplastic, benign-appearing bone in their periphery (Fig. 2). The cellular nodules contained medium-sized cells with moderately sized, relatively uniform nuclei. The cells were mostly polygonal and had abundant, variably eosinophilic, sometimes vacuolated cytoplasm. There was typically loose myxoid matrix between the tumor cells (Fig. 3). In some areas, the tu-
TABLE Antibodies Used in the Study Antibody
Dilution
Source
C A M 5.2 (specific for keratin 8) Keratin 1 9
1 : 10 1:50 1: 4 0 1:lO 1 : 12,800 1 : 100 1 :800 1 : 3,200 1:50
Beckton-Dickinson, Mountain View, CA Dakopatts, Carpinteria, CA Dakopatts Dakopatts Enzo Biochem, New York, NY Dakopatts Dakopatts Enzo Dakopatts
Epithelial membrane antigen Vimentin Muscle-specific actin IHHF-35) Oesmin (monoclonal D-33) S-100 protein (polyclonal) Melanoma-specific antigen (HMB-45) Factor VIII-related antigen
Intriguing Case: Chordomalike Soft Tissue Sarcoma
579
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closely apposed without significant cellular projections. In many cells, large vacuoles and multiple lipid droplets were present. Arrays of intermediate filaments were often seen, and some of these formed tonofilamentlike bundles. Glycogen particles often formed rosettelike groups (Fig. 6). Some cells were joined by desmosomelike cell-to-cell junctions (Fig. 7).
IMMUNOHISTOCHEMISTRY
FIG. 1 The tumor involves extensively the soft tissues around the knee, predominantly growing in the popliteal aspect. The proximal tibia is seen below and the femur above, 100% reduction. mor cells were spindle shaped but still relatively uniform (Fig. 4). Approximately 1 2 mitoses were seen per 10 high-power fields. Scattered lymphocytic infiltration was seen within the cellular nodules. Necrotic foci and hyalinized areas were commonly seen within the cellular nodules.
ELECTRON MICROSCOPY The tumor cells were oval t o polygonal and had moderately sized nuclei with a vesicular appearance and marginated chromatin. The cytoplasm was abundant with welldeveloped rough endoplasmic reticulum and multiple polyribosomes. Abundant collagen fibers were seen between tumor cells in some areas. Thus a significant number of tumor cells had fibroblastlike characteristics (Fig. 5). The cells in the central aspects of cellular nests were
A major proportion of tumor cells were cytokeratin-positive with CAM 5.2 antibody specific for keratin 8 (Fig. 8a). Keratin 1 9 immunostaining showed similar extensive positivity within the cellular nodules of the tumor, as did AEI antibody, which also reacts with keratin 19. AE8 antibody specific for keratin 1 3 was negative. The majority of the tumor cells were also positive for epithelial membrane antigen. The tumor cells were uniformly positive for vimentin (Fig. 8b). Muscle actin and desmin were only seen in the vessel walls or muscle elements outside the tumor tissue (Fig. 8c). A significant proportion of tumor cells (about 30%) was positive for S-100 protein (Fig. 8d). The 5-100 protein-positive areas were not morphologically different from the rest of the areas. Staining for melanomaspecific antigen (HMB-45 antibody) was negative. lmmunostaining for factor Vlll labeled vascular endothelium but not the tumor cells.
DISCUSSION The present soft tissue tumor from the knee area has features that necessitate considering several tumor entities seen in soft tissue and bone. The differential diagnoses are especially chordoma, ESMC (chordoid sarcoma), and the so-called parachordoma. Also, the diagnoses of malignant mixed tumor of sweat glands and metastatic carcinoma may be considered on the basis of immunohistochemical findings. The present tumor resembles chordoma in several respects. By light microscopy, the tumor cells show epitheliallike clustering, cytoplasmic vacuolization, and
M. Miettinen et a1
Ultrastruct Pathol Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
580
FIG. 2
The tumor consists of cellular nodules separated b y fibrous septa. Metaplastic bone is seen in the center. Hematoxylin and eosin, x 50.
myxoid extracellular matrix within the cellular lobules. Ultrastructurally observed desmosomelike junctions and bundles of filaments are similar t o those described in ~ h o r d o m almmunohistochemically .~ identified keratin, epithelial membrane antigen, and vimentin immunoreactivity is typically seen in chordoma.6-8Furthermore, the tumor showed S-I00 protein immunostaining, as is seen in chordoma.’ The extraskeletal location in the leg differs from the usual site of true chordoma, however, which is a neoplasm of the axial skeleton typically seen in the sacral area.’ Metastatic chordoma may be seen in peripheral locations. We have seen metastatic chordoma in skin of lower extremity, buttocks and chest wall, but not in deep locations in the lower extremity. In the present case, there was no history or evidence of chordoma in any primary location. We hold that this tumor is a soft tissue sarcoma closely
resembling chordoma, although w e are unable t o provide a satisfactory explanation for its histogenesis. In 1977 Dabska’ described a series of chordomalike peripheral soft tissue tumors seen in the extremities and the trunk and named these tumors parachordomas, which she thought formed an entity. By the light microscopic illustrations in Dabska’s report, parachordoma seems t o be morphologically unique tumor, often containing a biphasic pattern with small primitive cells forming solid clusters and cartilaginous areas resembling the biphasic structure of mesenchymal chondrosarcoma. Even true glandular structures resembling embryonal epithelia may be seen.’ The present tumor did not contain such elements. It also seems that parachordomas are clinically of a low-grade malignant nature compared with our fatal chordomalike sarcoma. The literature on
Ultrastruct Pathol Downloaded from informahealthcare.com by QUT Queensland University of Tech on 11/02/14 For personal use only.
FIG. 3 The neoplastic cells are polygonal, vacuolated, and relatively uniform. Hematoxylin and eosin, x 220.
FIG. 4 Some nests of tumor cells have a spindle-cell appearance. Hematoxylin and eosin, x 220.
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FIG. 5 Electron microscopy shows fibroblastlike characteristics in a number of tumor cells, which show abundant rough endoplasmic reticulum and are separated by collagenous intercellular material, x 10,400. parachordoma since then has been scant, and no ultrastructural or immunohistochemical data are available to compare parachordoma with other entities. A tumor called chordoma periphericum and believed to represent parachordorn? was reported by Povysil and Matejovsky. This was a bone tumor that arose in the tibia; no further clinical details were available. This tumor had a lobular histologic pattern, and electron microscopy showed multiple cytoplasmic vacuoles and an abundance of glycogen, features that resemble those of chordoma. No immunohistochemical data were available. ESMC, some variants of which apparently have been called chordoid sarcoma, has architectural features somewhat similar t o those of the present tumor. Both electron microscopic and immunohistochemical features of ESMC, however, seem to be at variance with our chordoma-
like sarcoma. ESMC is more closely related to chondrosarcoma than chordoma as suggested by electron microscopy, where ESMC shows scalloped cellular outlines and a lack of true desmosomes,4~”~’3 similar t o the ultrastructure of chondrosarcoma.’4 Also, immunohistochemical comparison with chordoma shows that ESMC does not have keratin^,^,'^ although epithelial membrane antigen has been described in some cases.” A case of intraosseous chordoid sarcoma from the scapulat6 contained prominent cytoplasmic lipid droplets and was considered a possible brown fat tumor. In retrospect, however, the histologic illustrations suggest a relationship with ESMC. One case of chordoid sarcoma from soft tissues of the posterior neck reported by Tanaka and Asao17 illustrates histologic features suggestive of chordoma with trabeculae of epitheliallike tumor cells in myx-
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Intriguing Case: Chordomalike Soft Tissue Sarcoma
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FIG. 6 Electron microscopy shows multiple lipid droplets and cytoplasmic intermediate filament bundles. Glycogen particles are also evident, x 10,400.
FIG. 7 Cell junctions are visible, some of which resemble desmosomes, x 34,200.
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584 M. Miettinen et a1
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Intriguing Case: Chordomalike Soft Tissue Sarcoma
oid matrix; electron microscopy described nonspecific features, and there was no mention about the presence or absence of desmosomes. No immunohistochemistry was available a t that time. The tumor was located extraosseously in the posterior neck, but because of its massive size it was close to the vertebral bones. Clear cell chondrosarcoma, although a bone tumor, can be considered in the differential diagnosis in the present case, but this tumor usually shows regular chondroid features as well and by electron microscopy has an unmistakable chondroid appearance with a scalloped outer membrane and cells floating in abundant loose matrix. Focusing on the prominent presence of epithelial markers, several other tumor types, especially synovial sarcoma, primary sweat gland carcinomas, and metastatic carcinomas, have to be considered in the differential diagnosis. Malignant mixed tumor (chondroid syringoma) arising in sweat glands of the skin can be theoretically considered in our case, but this was a massive deep soft tissue tumor with no apparent primary skin involvement (although subcutaneous nodules were present). Also, the present tumor did not have the glandular differentiation described in cutaneous malignant mixed tumors.” Finally, metastatic carcinoma, especially of renal origin, has t o be considered, although in our case the soft tissue tumor was clinically the primary disease manifestation with a long clinical duration. This and the lack of any clinical evidence of primary renal carcinoma make such a diagnosis most unlikely. 18r19
REFERENCES 1. Huvos A. Chordoma. In: Huvos A, ed. Bone Tumors. 2nd ed. Philadelphia: Saunders; 1991 : 599-624.
2. Dabska M. Parachordoma. A new clinicopathologic entity. Cancer. 1977;40:1586-1592. 3. Enzinger FM, Shiraki M. Extraskeletal myxoid chondrosarcoma. A n analysis of 34 cases. Hum Pathol. 1972:3:421-435. 4. Weiss SW. Ultrastructure of the so called “chordoid sarcoma.” Evidence supporting cartilaginous differentiation. Cancer. 1976;37:
300-306. 5. Erlandson RA, Tandler B, Lieberman PH, Higinbotham NL. Ultrastructure of human chordoma. Cancer Res. 1968;28:2115-2125. 6 Miettinen M, Lehto V-P, Dahl D, Virtanen I. Differential diagnosis of chordoma, chondroid and ependymal tumors as aided b y antiintermediate filament antibodies. A m J Pathol. 1983;1 12:160-169. 7 Abenoza P, Sibley RK. Chordoma: an immunohistologic study. Hum Pathol. 1986;17:744-
747. 8 Salisbury JR, lsaacson PG. Demonstration of cytokeratins and epithelial membrane antigen in chordomas and human fetal notochord. A m J Surg Pathol. 1985;9:791-797. 9 Nakamura Y, Becker LE, Marks A. 5100Protein in human chordoma and human and rabbit notochord. Arch Paihol lab Med. 1983;
107:l18-120. 10. Povysil C, Matejovsky Z. A comparative ultrastructural study of chondrosarcoma, chordoid sarcoma, chordoma and chordoma periphericum. Paihol Res Pract. 1985;179:546-559. 1 1 . Dardick I, Lgace R, Carlier MT, Jung RC. Chordoid sarcoma (extraskeletal myxoid chondrosarcoma). A light and electron microscope study. Virchows Arch Pathol Anat. 1983;399:
61-78. 12. Martin RF, Melnick PJ, Warner NE, Terry R, Bullock WK, Schwinn CP. Chordoid sarcoma. A m J Clin Pathol. 1973;59:623-635. 13. Pardo-Mindan FJ, Guillen FJ, Villas C, Vazquez JJ. A comparative ultrastructural study of chondrosarcoma, chordoid sarcoma, and chordoma. Cancer. 1981;47:2611-2619. 14. Erlandson RA, Huvos AG. Chondrosarcoma: a light and electron microscopic study. Cancer.
1974;34:1642-1652. 15. Wick MR, Burgess JH, Manivel JC. A reassessment of ”chordoid sarcoma.” Ultrastructural and immunohistochemical comparison w i t h chordoma and skeletal myxoid chondrosarcoma. M o d Pathol. 1988;1 :433-443. 16. Bender BL, Barnes L, Yunis EJ. lntraosseous “chordoid” sarcoma, chondroblastic or li-
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FIG. 8 lmmunohistochemical profile of chordomalike soft tissue sarcoma. (a) The tumor cells are uniformly positive for keratin 8, x 320. (b) Both the tumor cells and the fibrous stroma are vimentin positive, x 320. (c) The tumor is negative for muscle actins, which are present in vessel walls, x 160. (d) The tumor cell nests show S- 100 protein immunostaining, x 320.
M. M i e t t i n e n et a1
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poblastic origin? Virchows Arch Pathol Anat Histol. 1980;387:241-249. 17. Tanaka N, Asao T. Chordoid sarcoma of the soft tissue of the nape of the neck: a case with a 20-year follow-up. Virchows Arch Pathol Anat Histol. 1978;379:261-268. 18. Le Charpentier Y, Forest M, Postel M, Torneno 6,Abelanet R. Clear-cell chondrosarcoma. A report of five cases including ultrastructural study. Cancer. 1979;44:622-629. 19. Angervall L, Kindblom L-G. Clear-cell chondro-
sarcoma. A light- and electron-microscopic and histochemical study of t w o cases. Virchows Arch Pathol Anat Histol. 1980;389:27-
41. 20. Redono C, Rocamora A, Villoria F, Garcia M. Malignant mixed tumor of the skin: malignant 1690chondroid syringoma. Cancer. 1990;49:
1696. Accepted in revised form October 3, 1997.
