Department of Pathology, University of Oklahoma Health Sciences Center

June 2003, Case 306-3. Quiz set! Click here to see.

A 29 year-old Woman with a Mass in her Thigh

Adeboye O. Osunkoya, M.D. and Ravindranauth N. Sawh, M.B., B.S., D.M. (Path) Last update: June 30, 2003.

Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma

Clinical information: A 29 year-old woman presented with a 9 cm mass in the thigh without bone involvement. An excision yielded the following specimen.

Gross pathology of the case: 

    The tumor was lobulated and circumscribed. It had a fleshy gray-white, soft cut surface with scattered small foci that were more translucent than the surrounding tumor tissue.

Histopathology of the case: 

Com306-3-LM1.gif (95498 bytes) Com306-3-LM2.gif (97133 bytes) Com306-3-MM1.gif (93272 bytes) Com306-3-HM3.gif (132072 bytes) Com306-3-HM2.gif (98941 bytes) Com306-3-LM3.gif (134903 bytes) Com306-3-MM2.gif (131647 bytes) Com306-3-HM5.gif (122118 bytes)Click thumbnails to see pictures.

    At low power magnification (Panel A and B), the tumor seems to have two distinct components:

  1. A dark blue, highly cellular, background stroma; 
  2. Well-demarcated, pale blue islands of chondroid-appearing tissue. 

    Together, these two components impart a so-called "white clouds in blue sky" histologic appearance. At medium- and high power magnification (Panel C and D), the following histologic features are better appreciated:

  1. The lacunar nature of cells in the chondroid areas that confirms their cartilaginous nature;
  2. Impressive nuclear pleomorphism in the neoplastic chondrocytes (Panel D);
  3. Tightly packed, undifferentiated spindle cells in the background stroma (Panel E).

    Panels  F, G, and H are taken from a different area of the tumor and were not posted on the question web-page. The pathologic change in these areas are very common among mesenchymal chondrosarcoma and should be looked for. This area shows:

  1. Lobules of highly cellular tumor separated by fibrous connective tissue septa (Panel F);
  2. Prominent tumor vascularity with highly branching vessels which (with a bit of imagination!) resemble deer "antlers" or "staghorns"(Panel G and H).

    This pattern of vessel distribution is similar to that seen in hemangiopericytoma (an uncommon soft tissue tumor) and is therefore often described as a “hemangiopericytoma-like” vascular pattern. The overall gross and light microscopic features in this case are consistent with a diagnosis of primary extraskeletal mesenchymal chondrosarcoma.

DIAGNOSIS: Extraskeletal mesenchymal chondrosarcoma. 

Discussion: General Information    Pathology    Differential diagnosis

General Information    

    Mesenchymal chondrosarcoma is a rare malignant neoplasm that was first described as a distinct pathologic entity in 1959 by Lichtenstein and Bernstein 1. Histologically, the tumor is characterized by a bimorphic growth pattern in which islands of usually well-differentiated hyaline cartilage are surrounded by sheets of primitive mesenchymal cells often with hemangiopericytoma -like components 2.  Biologically, different stages of cartilaginous differentiation have been demonstrated in mesenchymal chondrosarocoma by phenotypic studies 3. Clinical features that distinguish mesenchymal chondrosarcoma from other cartilaginous malignancies include occurrence in young patients, increased tendency to occur in the head and neck areas, and increased tendency to occur as entirely extraskeletal lesions.

    Epidemiologically, mesenchymal chondrosarcoma represents less than 2% of all cartilaginous malignancies 4 and typically affects patients in the second and third decades of life, i.e. adolescents and young adults. However, the tumor has also been reported to occur in infants and young children 2, 5, 6, 7. Males and females are involved in equal proportion. Mesenchymal chondrosarcoma may arise in both skeletal and extraskeletal locations, with the former being more common than the latter. Skeletal tumors typically involve the jaws and ribs 4, 8, 9 whereas extraskeletal tumors most often occur in the head and neck region, including the orbit 10, 11 and meninges 6, 12, and in the lower extremities, with the thigh being the most common site 13. However, the tumor has also been reported in a variety of unusual sites, including the heart 14, femoral vein 15, lung 16, and kidney 17.

    Clinical symptoms vary, depending on the site of involvement and whether the lesion is skeletal or extraskeletal. However, pain and swelling lasting more than one year is typical. Radiologically, skeletal lesions are primarily lytic and destructive with poor peripheral margins. Cortical destruction with breakthrough, and extraosseous extension into soft tissue, are common. Chondroid type calcifications and foci of low signal intensity with enhancing lobules are also seen. Most extraskeletal mesenchymal chondrosarcomas are deep seated tumors with more than two third of them occur in the thigh, particularly the popliteal fossa 17. Radiographically, they do not have distinctive features that allows differentiation from other sarcomas.

    Mesenchymal chondrosarcoma is a highly aggressive tumor. In general, they have a metastatic rate higher than other cartilaginous malignancies and has an increased tendency to metastasize to the brain, lung, and liver. Metastasis to the lung is most common. Surgical treatment involves wide or radical resection of the lesion. Adjuvant radiation therapy has been employed for some high grade lesions, but systemic chemotherapy has had little or no success. The long-term prognosis is generally poor with 5- and 10-year survival rates of about 50% and 25%, respectively 16, 17. 

Pathology    

    Grossly, mesenchymal chondrosarcoma typically appears as a circumscribed, lobulated, solid mass with a soft, fleshy, grey-white to gray-pink cut surface. Scattered deposits of cartilage and/or bone of varying size may be grossly recognized, and areas of hemorrhage and necrosis may be present. Tumor size is variable with reported tumor diameters ranging from 3 - 37 cm. Microscopically, mesenchymal chondrosarcomas are biphasic tumors composed of sheets of round to spindle-shaped primitive mesenchymal cells surrounding discrete islands of hyaline cartilage 16, 17. The proportions of primitive and cartilaginous elements vary widely among tumors and even within different areas of the same tumor. Cartilaginous differentiation ranges in degree and extent from small foci with high grade nuclear features to large areas of well differentiated cartilage 16. The primitive mesenchymal component is highly vascular, typically containing large numbers of highly branched vascular channels (the so-called “hemangiopericytoma-like pattern”).

    Immunohistochemically, the cartilaginous areas are indistinguishable from other forms of chondrosarcoma 17. A wide range of low- to high-level of differentiation can be seen. Phenotypic studies have also demonstrated a range of differentiation 3. The cartilaginous component typically staining strongly for S-100 protein.  However, only isolated cells in the undifferentiated areas stain for this antigen. The small cell component of mesenchymal chondrosarcoma is immunoreactive for vimentin and CD99. In over 50% of cases, all components of the tumor i.e. small cells, lacunar chondroblasts, and chondroid matrix, stain for Leu-7 18. Recently, an antibody raised against Sox9, a transcription factor considered to be a “master regulator” of chondrogenesis, was reported to be positive in both the primitive mesenchymal and the cartilaginous components of 21/22 mesenchymal chondrosarcomas tested, while being negative in a total of 68 other “small round blue cell tumors" 19. There are few published cytogenetic studies of mesenchymal chondrosarcoma. Recently, translocations involving chromosomes 13 and 21 [der(13;21)(q10;q10)] have been demonstrated in three tumors (two skeletal, one extraskeletal), possibly representing a chromosomal rearrangement characteristic of this neoplasm 20. However, a single case of mesenchymal chondrosarcoma has also been reported to show the reciprocal translocation t(11;22)(q24;q12) typical of Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (pPNET) 21, suggesting a possible relationship with this entity.

Differential diagnosis

    The histologic differential diagnosis of mesenchymal chondrosarcoma is broad, and includes dedifferentiated chondrosarcoma, Ewing's sarcoma, embryonal rhabdomyosarcoma, hemangiopericytoma, synovial sarcoma, small cell osteosarcoma, and non-Hodgkin lymphoma.

    Dedifferentiated chondrosarcoma typically occurs in an older age group and is more likely to affect the appendicular skeleton. These tumors show an abrupt transition between the low grade chondroid component and the high grade dedifferentiated component. A hemangiopericytoma-like vascular pattern is not a feature. Ewing's sarcoma lacks a chondroid component, and tumor cells are typically S-100 protein-negative, unlike mesenchymal chondrosarcoma. Reciprocal translocation between chromosomes 11 and 22 involving bands q24 and q12, t(11;22)(q24;q12), occurs in approximately 90% of Ewing’s sarcomas, pPNETs and Askin’s tumors 22. Embryonal rhabdomyosarcoma lacks a chondroid component and consistently expresses muscle differentiation markers such as desmin, muscle specific actin, and myoglobin. Although hemangiopericytoma and synovial sarcoma may contain areas with vascular architecture similar to that of mesenchymal chondrosarcoma, they lack the chondroid component.  Small cell osteosarcoma is typically negative for S-100 protein and have bone formation. Non-Hodgkin lymphomas are positive for leucocyte common antigen (LCA) and they also lack the chondroid component.

Reference: 

  1. Lichtenstein L, Bernstein D. Unusual benign and malignant chondroid tumors of bone: a survey of some mesenchymal cartilage tumors and malignant chondroblastic tumors including a few multricentric ones and chondromyxoid fibromas. Cancer 1959 12:1142-57.
  2. Dabska M, Huvos AG. Mesenchymal chondrosarcoma in the young. Virchows Arch A Pathol Anat Histopathol. 1983 399:89-104.
  3. Aigner T, Loos S, Muller S, Sandell LJ, Unni KK, Kirchner T. Cell differentiation and matrix gene expression in mesenchymal chondrosarcomas. Am J Pathol 2000 156:1327-35.
  4. Nakashima Y, Unni KK, Shives TC, Swee RG, Dahlin DC. Mesenchymal chondrosarcoma of bone and soft tissue. A review of 111 cases. Cancer 1986 57:2444-53.
  5. Crawford JG, Oda D, Egbert M, Myall R. Mesenchymal chondrosarcoma of the maxilla in a child. J Oral Maxillofac Surg 1995 53:938-41.
  6. La Spina M, Dollo C, Giangaspero F, Bertolini P, Russo G. Intracranial mesenchymal chondrosarcoma with osteoid formation: report of a pediatric case. Childs Nerv Syst 2003  April 17(Epub ahead of print).
  7. Crosswell H, Buchino JJ, Sweetman R, Reisner A. Intracranial mesenchymal chondrosarcoma in an infant. Med Pediatri Oncol 2000 34:370-4.
  8. Vencio EF, Reeve CM, Unni KK, Nascimento AG. Mesenchymal chondrosarcoma of the jaw bones: clinicopathologic study of 19 cases. Cancer 1998 82:2350-5.
  9. Takahashi K, Sato K, Kanazawa H, Wang XL, Kimura T. Mesenchymal chondrosarcoma of the jaw: report of a case and review of 41 cases in the literature. Head Neck 1993 15: 459-64.
  10. Kashyap S, Sen S, Betharia SM, Dada VK. Mesenchymal chondrosarcoma of the orbit: a clinicopathological study. Orbit 2001 20:63-67.
  11. Khouja N, Ben Amor S, Jemel H, Kchir N, Boussen H, Khaldi M. Mesenchymal extraskeletal chondrosarcoma of the orbit. Report of a case and review of the literature. Surg Neurol 1999 52:50-53.
  12. Demirtas E, Ersahin Y, Yilmaz F, Mutluer S, Veral A. Intracranial meningeal tumors in childhood; a clinicopathologic study including MIB-1 immunohistochemistry. Pathol Res Pract 2000 196:151-8.
  13. Leggon RE, Munro M, Schuerch C. Thigh mass in a 52-year-old woman. Clin Orthop 2001;388:252-7, 260-3.
  14. Nesi G, Pedemonte E, Gori F.  Extraskeletal mesenchymal chondrosarcoma involving the heart; report of a case. Ital Heart J 2000 1:435-7.
  15. Kim GE, Kim do K, Park IJ, Ro JY. Mesenchymal chondrosarcoma originating from the femoral vein. J Vasc Surg 2003 37202-5.
  16. Dorfman HD, Czerniak B. Malignant cartilage tumors. In Bone Tumors, St. Louis, 1998, Mosby;353-440.
  17. Weiss SW, Goldblum JR. Cartilaginous soft tissue tumors. In Enzinger and Weiss’s Soft Tissue Tumors, 4th edt. Mosby, St. Louis, 2001, pp. 1361-88.
  18. Swanson PE, Lillemoe TJ, Manivel JC, Wick MR. Mesenchymal chondrosarcoma. An immunohistochemical study. Arch Pathol Lab Med 1990 114:943-8.
  19. Wehrli BM, Huang W, De Crombrugghe B, Ayala AG, Czerniak B. Sox9, a master regulator of chondrogenesis, distinguishes mesenchymal chondrosarcoma from other small blue round cell tumors. Human Pathol 2003 34:263-9.
  20. Naumann S, Krallman PA, Unni KK, Fidler ME, Neff JR, Bridge JA. Translocation der(13;21)(q10;q10) in skeletal and extraskeletal chondrosarcoma. Mod Pathol 2002 15:572-76.
  21. Sainati L, Scapinello A, Montaldi A, Bolcato S, Ninfo V, Carli M, Basso G. A mesenchymal chondrosarcoma of a child with the reciprocal translocation (11;22)(q24;q12). Cancer Genet Cytogenet 1993 71:144-7.
  22. Dorfman HD, Czerniak B. Ewing's sarcoma and related entities. In Bone Tumors, St. Louis, 1998, Mosby; pp. 607-659.

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