Close

References

  1. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER stat fact sheets: bone and joint cancer. Available at: http://seer.cancer.gov/statfacts/html/bones.html. Accessed January 20, 2016.
  2. American Cancer Society. Bone cancer: detailed guide. Revised January 21, 2016. Available http://www.cancer.org/cancer/bonecancer/detailedguide/bone-cancer-what-is-bone-cancer. Accessed January 21, 2016.
  3. ESMO/European Sarcoma Network Working Group. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep;25 (suppl 3):iii113-23. PMID: 25210081
  4. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines). Bone cancer. Version 2.2016. Available at: http://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. Accessed: January 20, 2016.
  5. Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F, eds. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Geneva, Switzerland: WHO Press; 2013.
  6. Ortner DJ. Differential diagnosis and issues in disease classification. In: Grauer AL, ed. A Companion to Paleopathology. Chichester, West Sussex, UK: John Wiley & Sons; 2016: chapter 14.
  7. Huang AJ, Willis MH, Kattapuram SV, Bredella MA. Surgical staging 2: metastatic disease. In: Davies AM, Sundaram M, James SJ, eds. Imaging of Bone Tumors and Tumor-Like Lesions: Techniques and Applications. Berlin, Germany: Springer Verlag; 2009: chapter 10.
  8. National Cancer Institute. Bone cancer. Reviewed March 13, 2008. Available at: http://www.cancer.gov/types/bone/bone-fact-sheet. Accessed January 20, 2016.
  9. Heymann D, ed. Bone Cancer: Primary Bone Cancers and Bone Metastases. 2nd ed. San Diego, CA: Elsevier; 2015: chapters 1, 26, 32.
  10. National Cancer Institute. Osteosarcoma and malignant fibrous histiocytoma of bone treatment–for health professionals (PDQ). Updated: December 8, 2015. http://www.cancer.gov/types/bone/hp/osteosarcoma-treatment-pdq. Accessed January 20, 2016.
  11. Edge SB, Byrd DR, Compton CC, et al, eds. American Joint Committee on Cancer (AJCC) Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010.
  12. Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res. 1986 Mar;(204):9-24. PMID: 3456859
  13. Bovee JVMG, de Andrea CE. Bone tumors. In: Mills SE, ed. Sternberg's Diagnostic Surgical Pathology. Vol I. 6th ed. Philadelphia, PA: Wolters Kluwer Health; 2015: chapter 8.
  14. O'Donnell P. Chondrosarcoma. Orthobullets.com. Updated March 4, 2015. Available at: http://www.orthobullets.com/pathology/8023/chondrosarcoma. Accessed January 21, 2016.
  15. Lakshmanan P, Jennings PG, Dharmarajan D. Chondrosarcoma. Medscape Drugs & Diseases from WebMD. Updated April 21, 2014. Available at: http://emedicine.medscape.com/article/1258236-overview. Accessed January 21, 2016.
  16. American Cancer Society. Ewing family of tumors: detailed guide. Revised October 2, 2014. Available http://www.cancer.org/cancer/ewingfamilyoftumors/detailedguide/ewing-family-of-tumors-detailed-guide-toc. Accessed January 21, 2016.
  17. Murphey MD, Senchak LT, Mambalam PK, Logie CI, Klassen-Fischer MK, Kransdorf MJ. From the radiologic pathology archives: Ewing sarcoma family of tumors: radiologic-pathologic correlation. Radiographics. 2013 May;33(3):803-31. PMID: 23674776
  18. O'Donnell P. Ewing's sarcoma. Orthobullets.com. Updated November 28, 2014. Available at: http://www.orthobullets.com/pathology/8047/ewings-sarcoma. Accessed January 21, 2016.
  19. Abbasi D. Chordoma. Orthobullets.com. Updated May 6, 2014. Available at: http://www.orthobullets.com/pathology/8032/chordoma. Accessed January 21, 2016.
  20. Doyle LA. Sarcoma classification: an update based on the 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone. Cancer. 2014 Jun 15;120(12):1763-74. PMID: 24648013
  21. Dickey ID. Fibrosarcoma. Medscape Drugs & Diseases from WebMD. Updated November 20, 2014. Available at: http://emedicine.medscape.com/article/1257520-overview. Accessed January 21, 2016.
  22. Moore D. Fibrosarcoma of bone. Orthobullets.com. Updated January 2, 2015. Available at: http://www.orthobullets.com/pathology/8031/fibrosarcoma-of-bone. Accessed January 21, 2016.
  23. McCarthy EF. Fibroblastic and fibrohistiocytic tumors. In: Folpe AL, Inwards CY, eds. Bone and Soft Tissue Pathology. Philadelphia, PA: Saunders; 2010: chapter 16.
  24. Nystrom LM, Buckwalter JA, Syrbu S, Miller BJ. Serum protein electrophoresis in the evaluation of lytic bone lesions. Iowa Orthop J. 2013;33:114-8. PMID: 24027470
  25. Gounder MM. Bone sarcoma guidelines. Medscape Drugs & Diseases from WebMD. Updated June 25, 2015. Available at: http://emedicine.medscape.com/article/2500013-overview. Accessed January 22, 2016.
  26. Cripe TP. Pediatric osteosarcoma. Medscape Drugs & Diseases from WebMD. Updated October 21, 2015. Available at: http://emedicine.medscape.com/article/988516-treatment. Accessed January 22, 2016.
  27. National Cancer Institute. Ewing sarcoma treatment–for health professionals (PDQ). Updated: November 9, 2015. http://www.cancer.gov/types/bone/hp/ewing-treatment-pdq. Accessed January 22, 2016.

Image Sources

  1. Slide 1: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137725/. Accessed January 15, 2016.
  2. Slide 2: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592482/ (left); https://commons.wikimedia.org/wiki/File:Paget%27s_disease_R_coxal.jpg (right). Both accessed January 15, 2016.
  3. Slide 3: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826297/. Accessed January 15, 2016.
  4. Slides 4, 5, and 29: http://seer.cancer.gov/statfacts/html/bones.html. Accessed January 15, 2016.
  5. Slide 6 and 18: http://emedicine.medscape.com/article/1256857-overview. Accessed January 15, 2016.
  6. Slide 7: http://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. Accessed January 15, 2016.
  7. Slide 8: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711896/. Accessed January 15, 2016.
  8. Slide 9: https://commons.wikimedia.org/wiki/File%3AMrichondrosarcoma.jpg (left); https://commons.wikimedia.org/wiki/File:Chondrosarcoma_(1).jpg (right). Both accessed January 15, 2016.
  9. Slides 10-14: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644679/. Accessed January 15, 2016.
  10. Slide 15: https://commons.wikimedia.org/wiki/File:Chordom_Computertomographie_sagittal.jpg (left); https://commons.wikimedia.org/wiki/File:Chordoma_-_very_high_mag.jpg (right). Both accessed January 15, 2016.
  11. Slides 16 and 27: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726520/ (left); https://visualsonline.cancer.gov/details.cfm?imageid=2137 (right). Both accessed January 15, 2016.
  12. Slide 17: https://commons.wikimedia.org/wiki/File:Blausen_0097_BoneMarrowBiopsy.png. Accessed January 15, 2016.
  13. Slide 19: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642001/. Accessed January 15, 2016.
  14. Slides 20 and 21: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234849/. Accessed January 15, 2016.
  15. Slides 22 and 23: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090394/. Accessed January 15, 2016.
  16. Slides 24 and 25: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418025/. Accessed January 15, 2016.
  17. Slide 26: https://en.wikipedia.org/wiki/File:Sacral_Bone_Chordoma_(%CE%A7%CF%8C%CF%81%CE%B4%CF%89%CE%BC%CE%B1_%CF%84%CE%BF%CF%85_%CE%99%CE%B5%CF%81%CE%BF%CF%8D_%CE%BF%CF%83%CF%84%CE%BF%CF%8D).jpg. Accessed January 15, 2016.
  18. Slide 28: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947724/. Accessed January 15, 2016.
Close

Contributor Information

Author

Ali Ahmad, MD
Complex General Surgical Oncology Fellow
Roger Williams Medical Center
Providence, Rhode Island

Disclosure: Ali Ahmad, MD, has disclosed no relevant financial relationships.

Contributor

Vera Ruvinskaya, MS

Disclosure: Vera Ruvinskaya, MS, has disclosed no relevant financial relationships.

Editor

Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York

Disclosure: Olivia Wong, DO, has disclosed no relevant financial relationships.

Loading...

Close<< Medscape

5 Bone Sarcomas: Rare, Heterogeneous, and often Curable

Ali Ahmad, MD  |  January 27, 2016

Close
Swipe to advance
Slide 1

Primary bone cancers are rare tumors, accounting for an estimated 0.2% of all malignancies.[1-4] They are considered a subcategory of sarcomas, which derive from connective tissues and thus occur in the bones, cartilage, fat, muscle, and other tissues.[2,5,6] Bone sarcomas can occur in any of the bones of the body, but most involve the skeletal long bones.[3]

This heterogeneous group of tumors is further subclassified by the tissue of origin, with the three most common types as follows[2,7,8]:

  • Osteosarcomas, or osteogenic sarcomas (arise from bone): 35%
  • Chondrosarcomas (arise from cartilage): 30%
  • Ewing sarcoma (uncertain origin): 16%

Other, more rare forms of bone sarcomas (1%-5%) include the following[2,7-9]:

  • Chordomas (arise from cellular remnants of the notochord)
  • Fibrosarcomas (arise from fibrogenic tissue)
  • Malignant fibrous histiocytoma, or pleomorphic sarcoma (uncertain origin)
  • Giant cell tumors, or osteoclastomas (arise from giant cells of bone)
  • Adamantinomas (arise from epithelial cells)

The intraoperative photo shows a low-grade chondrosarcoma of the distal femur delimited by K-wires (arrows). The inset image shows the surgical specimen after resection with a K-wire resected en bloc.

Images courtesy of Zoccali C, Rossi B, Ferraresi V, Anelli V, Rita A, and the Regina Elena National Cancer Institute. BMC Surg. 2014;14:52. [Open access.] PMID: 25123066,PMCID: PMC4137725.

Slide 2

Risk Factors

The etiology and pathophysiology of primary bone cancer remain unclear, with the majority of bone sarcomas occurring sporadically and without any identifiable predisposition.[2,4,8] However, known risk factors for these malignant tumors include the following conditions[2,4,8]:

  • Paget disease: This is a chronic disorder characterized by thick brittle bones secondary to disorganized bone remodeling, typically affecting the pelvis, femur, and lower lumbar vertebrae. Paget disease has been associated with the development of osteosarcoma in approximately 1% of individuals.
  • Multiple enchondromatosis (Ollier disease): The presence of multiple benign cartilage tumors (enchondromas) appears to increase the risk for developing chondrosarcomas.
  • Radiation: Exposure to high-dose radiation, especially in childhood, can significantly increase the risk of developing secondary bone sarcomas. Build-up of radioactive minerals such as radium or strontium can occur and may also predispose to the development of malignant skeletal neoplasms.
  • Bone marrow transplantation (BMT): Individuals who have undergone BMT for the treatment of another condition may be at an increased risk for developing osteosarcoma.

The plain radiograph on the left is from a young patient with Ollier disease. Multiple enchondromas involving the distal radius can be seen (arrow). The plain radiograph on the right is from an elderly patient with Paget disease of the bone. The arrows show disorganized bone formation of the right hemi-pelvis.

Images courtesy of (1) Dr Fitoussi, Hôpital Robert Debré, Paris, France, via Silve C, Juppner H. Orphanet J Rare Dis. 2006;1:37. [Open access.] PMID: 16995932, PMCID: PMC1592482 (left); and (2) Wikimedia Commons/Jmarchn (right).

Slide 3

Genetic syndromes

Several hereditary syndromes caused by gene mutations are also considered risk factors for primary bone cancers, such as the following:

  • Osteosarcoma: Li-Fraumeni syndrome (TP53, CHEK2) (children), Rothmund-Thompson syndrome (RTS) (children) (shown), retinoblastoma (RB1) (children), Paget disease (LOH18CR1) (adults >50 years), Bloom syndrome (BLN) (any age), Diamond-Blackfan anemia (children <1 year), and Werner syndrome (WRN) (age, 20s) have been associated with a predisposition to osteosarcoma.[2,8,10]
  • Chondrosarcoma: Multiple exostoses syndrome (or, multiple osteochondromas syndrome) (EXT1, EXT2, EXT3) (children <12 years) has been associated with an increased risk of developing chondrosarcoma.[2]

Some osteosarcomas and chordomas appear in families, but an identifiable genetic mutation has not yet been found.[2]

Images A-D demonstrate poikiloderma in patients with Rothmund-Thompson syndrome.

Image E shows distributed poikiloderma and valgism of the knees in a patient with Rothmund-Thompson syndrome.

Image F reveals thumb aplasia in the patient in image B.

Image G demonstrates radiographic bone defects in the patient in image E. A cystic-like destructive lesion of the humerus (distal epiphysis) is noted.

Images courtesy of Larizza L, Roversi G, Volpi L. Orphanet J Rare Dis. 2010;5:2. [Open access.] PMID: 20113479, PMCID: PMC2826297.

Slide 4

Incidence and Mortality

In the United States, primary bone cancer ranks as the 29th among the most common cancer types.

In 2016, the American Cancer Society (ASC) estimates there will be approximately 3,300 new US cases of bone and joint cancer—representing an estimated 0.2% of all new US cancer cases—with about 1,490 deaths (0.3% of all cancer deaths) from this disease.[1,2]

Data from the Surveillance, Epidemiology, and End Results (SEER) Program from 2010 to 2012 indicate about 0.1% of men and women will be diagnosed with bone and joint cancer in their lifetime.[1]

Image courtesy of the National Cancer Institute (NCI)/SEER Program.[1]

Slide 5

The incidence of bone and joint cancer has increased an average rate of 0.4% annually over the last decade, with mortality declining at an average rate of 0.3% between 2003 and 2012.[1]

The pediatric population (<20 years) (27.6%) is disproportionately affected, followed by those aged 55-64 years (12.6%) and 45-54 years (12.3%).[1] The median age at diagnosis is 42 years. Men are affected slightly more commonly than women, as are white, non-Hispanic white, and Hispanic individuals compared to those of other races/ethnicities.[1] American Indian/Alaska Native populations are the least affected.

Adults with primary bone tumors are most often diagnosed with chondrosarcomas (>40%), followed by osteosarcomas (28%), chordomas (10%), Ewing tumors (8%), and malignant fibrous histiocytoma/fibrosarcomas (4%).[2]

In children and adolescents, osteosarcomas (56%) are the most common primary bone cancers, followed by Ewing tumors (34%). An estimated 6% of children and adolescents develop chondrosarcoma (6%).[2]

Image courtesy of the NCI/SEER Program.[1]

Slide 6

Presentation

Localized pain is the most common sign of bone sarcomas,[2,3,8] and it may become more noticeable with growth of the tumor. Pain may be accompanied by the presence of swelling or a mass. In addition, as the bone cortex becomes compromised by the tumor, the affected bone becomes increasingly fragile and prone to pathologic fractures. If the tumor involves a joint, limitation of the range of motion or joint weight-bearing capacity may occur.[2] As is the case with other malignant neoplasms, unintentional weight loss and fatigue can occur.

Patients with nonmechanical pain or swelling in or near a bone that persists for more than a few weeks should undergo further immediate evaluation.[2,3,8]

The left image shows an osteosarcoma presenting as an asymmetric right shoulder mass in an adolescent patient. The right image is a plain radiograph that reveals a proximal humeral osteosarcoma (arrow) in the same patient.

Images courtesy of Medscape/Charles T Mehlman, DO, MPH.

Slide 7

Classification and Staging

Patients with suspected primary bone tumors should be evaluated and managed by an expert multidisciplinary team with experience in treating these neoplasms.[3,4]

As noted earlier, primary bone tumors are a subcategory of sarcomas,[2,5,6] on the basis of the World Health Organization (WHO) classification of bone and soft-tissue tumors.[5]

Several staging systems exist for bone tumors. The National Comprehensive Cancer Network (NCCN) follows the tumor/node/metastasis (TNM) staging classification of the American Joint Committee on Cancer (AJCC)[4,11] as well as the Surgical Staging System from the Musculoskeletal Tumor Society (MTS).[4,12] The European Society for Medical Oncology (ESMO) guidelines do not provide a specific recommendation for which system should be followed.[3]

Adapted image courtesy of the NCCN.[4]

Slide 8

Osteosarcoma

Osteosarcoma, also known as osteogenic sarcoma, is the most common primary bone cancer,[2,4,7,8] occurring predominantly in individuals aged 10-30 years, with males affected more than females.[2,4] The tumors generally arise as solitary lesions within the long bones of children, frequently involving the distal femur, proximal tibia, and proximal humerus.[2,4,13] Osteosarcoma often metastasizes to the lung, which has an associated high mortality.

On gross examination, the tumor is a white or reddish mass, lardaceous, and firm at an early disease stage; advanced tumors have a softened cortex with a white or straw-colored viscid consistency.[13]

Histologically, osteosarcoma is separated into central (medullary) tumors (conventional central, telangiectatic, intraosseous well differentiated [low grade], and small cell), as well as surface (peripheral) tumors (parosteal [juxtacortical] well differentiated [low grade], periosteal, and high-grade surface).[4,10] Conventional osteosarcomas show nuclear pleomorphism, hyperchromasia, and abundant mitoses.[13]

The images reveal a localized osteosarcoma that was complicated by pathologic fracture of the humerus in an adolescent patient.

Image a is an anteroposterior (A-P) radiograph of the patient at presentation.

Image b is a preoperative magnetic resonance image (MRI) demonstrating the extraosseous lesion and an undisplaced humeral fracture.

Image c shows the resected specimen, including the proximal humerus and biceps at the osteotomy level.

Image d shows reconstruction with a semi-shoulder prosthesis.

Image e is a postoperative radiograph of the affected arm with the prosthesis in place.

Images courtesy of Zuo D, Zheng L, Sun W, Hua Y, Cai Z. World J Surg Oncol. 2013;11:148. [Open access.] PMID: 23799947, PMCID: PMC3711896.

Slide 9

Chondrosarcoma

Chondrosarcoma is a collective term used for a heterogeneous group of tumors that consist predominantly of cartilage and range from low-grade tumors with low metastatic potential to high-grade, aggressive tumors characterized by early metastasis.[2,3,4,13] It is the second most common type of bone sarcoma,[2,4,7,8,13] primarily occurring in individuals in their third to sixth decade of life. Males and females are equally affected.

Chondrosarcoma may be primary (arise de novo) or secondary (arise from preexisting benign cartilage lesions) tumors, involving the metaphyseal region of the long bones (humerus, femur) as well as the flat bones of the pelvis, rib, and scapula.[2-4] These primary bone malignancies include the following subtypes[2,4,13]:

  • Conventional (about 75%-85% of all chondrosarcomas)[4,13]
  • Dedifferentiated
  • Clear cell
  • Mesenchymal
  • Parosteal
  • Secondary

On gross examination, the lesion is typically translucent, lobular, and blue-grey or white.[13]

Histologically, conventional low-grade chondrosarcomas appear bland, have few mitotic figures, and show enlarged chondrocytes with multinucleated lacunae.[14] Intermediate-grade tumors contain cartilage cells with enlarged, round nuclei as well as prominent nucleoli and cytoplasm consisting of prominent rough cytoplasmic reticula, mitochondria, and large amounts of glycogen.[15] High-grade tumors are characterized by high cellularity, prominent nuclear atypia, and mitosis.[15]

The pelvic MRI on the left reveals the classic lobulated appearance of a chondrosarcoma (arrow) in a 26-year-old patient. The histologic image on the right is from a chest-wall chondrosarcoma specimen in a different patient (hematoxylin and eosin [H&E] stain).

Images courtesy of Blake JK Young (left) and KGH (right), both via Wikimedia Commons.

Slide 10

Ewing Sarcoma

The Ewing sarcoma family of tumors includes Ewing sarcoma, peripheral primitive neuroectodermal tumor (PNET), PNET of bone, extraosseous Ewing sarcoma, and Askin tumor (PNET of the chest wall).[4,16] These tumors are treated similarly on the basis of their clinical presentation (eg, metastatic or localized) rather than their histologic subtype.[4,16]

Ewing sarcoma is the third most common form of bone sarcoma[2,7-9] and the second most common in the pediatric population and young adults, with a slight male predominance.[2,13] The majority arises from bones of the pelvis, chest wall (ribs, scapulae), tibia, femur, and humerus; however, other tissues and organs can be involved.[2-4]

The photographs are from the initial examination in a patient with Ewing sarcoma. The left photograph reveals right-side submandibular swelling. The right photograph is an intraoral image in the same patient showing the tumor mass coming from the mandible, as well as infiltrating the gingiva and the mouth floor.

Images courtesy of Gosau M, Baumhoer D, Ihrler S, Kleinheinz J, Driemel O. Head Face Med. 2008;4:24. [Open access.] PMID: 18983686, PMCID: PMC2644679.

Slide 11

The axial (left) and coronal (right) MRIs are from the same patient with Ewing sarcoma seen in the previous slide.

These images reveal an osteolytic mass measuring approximately 7 × 8 × 6 cm3 surrounding the mandible, with massive infiltration into the soft tissue of the mouth floor and the tongue.

Images courtesy of Gosau M, Baumhoer D, Ihrler S, Kleinheinz J, Driemel O. Head Face Med. 2008;4:24. [Open access.] PMID: 18983686, PMCID: PMC2644679.

Slide 12

The radionuclide images are from the same patient with Ewing sarcoma as in the previous two slides.

These 18-fluorodeoxyglucose (18F) positron emission tomography (PET) scans demonstrate enhancement in the right floor of the mouth, with expansion over the midline. There was no further enhancement visible in a whole-body scan (not shown).

Images courtesy of Gosau M, Baumhoer D, Ihrler S, Kleinheinz J, Driemel O. Head Face Med. 2008;4:24. [Open access.] PMID: 18983686, PMCID: PMC2644679.

Slide 13

The gross appearance of Ewing sarcomas is generally soft-grey to white, with margins that may be well or ill defined; extensive involvement of the medulla and cortex and periosteal elevation are common.[17] The lesions can also look necrotic or resemble pus.[18]

The gross specimen is from a mandibular resection in the same patient with Ewing sarcoma as in the previous three slides.

Image courtesy of Gosau M, Baumhoer D, Ihrler S, Kleinheinz J, Driemel O. Head Face Med. 2008;4:24. [Open access.] PMID: 18983686, PMCID: PMC2644679.

Slide 14

On histologic examination, typical Ewing sarcoma demonstrates undifferentiated, uniform, small, round blue cells with prominent round nuclei and fine chromatin.[13,17,18] There is scant cytoplasm, which contains glycogen. A rosette or pseudo-rosette pattern may be present.[17,18]

The micrographs are from the same patient with Ewing sarcoma as in the previous four slides.

Images a-c: Sheets of uniform and densely packed small cells show round nuclei with finely granular nuclear chromatin (H&E stain; at 200× and 400× magnification; images a and b, respectively) and lack of reticulin fibers (Novotny reticulin stain; at 400× magnification; image c).

Images d and e: The proliferation index is high (approximately 80% of cells showing immunoreactivity against MIB1) (image d; at 400× magnification) and the tumor cells demonstrate strong positivity for CD99 (image e; at 630× magnification).

Image f: Fluorescence in situ hybridization (FISH) analysis using an EWSR1(22q12) dual color break apart rearrangement probe. Tumor cells with separate orange and green signals indicate t(11;22)(q24;q12) can be seen (at 630× magnification).

Images courtesy of Gosau M, Baumhoer D, Ihrler S, Kleinheinz J, Driemel O. Head Face Med. 2008;4:24. [Open access.] PMID: 18983686, PMCID: PMC2644679.

Slide 15

Chordoma

Chordomas are rare primary bone cancers that arise from notochordal remnants to involve the sacrum (50%-60%), skull base (25%-35%), and vertebral column (15%-20%).[3,4,13] The tumors tend to be slow growing, with a low risk of distant metastases, but they are also locally aggressive with high chance of recurrence if incompletely excised.[2-4] Extraskeletal lesions occur but are extremely rare.[3,4]

Chordomas most frequently occur in adults older than 30 years (disproportionately affecting men), although any age can be affected.[2,13] They rarely occur in black persons.[13]

The gross appearance of typical chordomas is a lobular and gelatinous tumor.[19]

Histologically, the tumor cells are often separated by fibrous septa and have a characteristic foamy, multi-vacuolated appearance, with prominent nuclei and scant/absent mitotic activity.[13,19]

The sagittal computed tomography (CT) scan of the pelvis (left) shows a chordoma at the coccyx (asterisk). The micrograph (right) shows a very high magnification view of a chordoma (hematoxylin, phloxine and saffron [HPS] stain).

Images courtesy of Hellerhoff (left) and Nephron (right), both via Wikimedia Commons.

Slide 16

Fibrosarcoma

Fibrosarcoma of bone is a diagnosis of exclusion on the basis of the 2013 update of the WHO classification of soft-tissue and bone tumors. It is defined as an intermediate- to high-grade spindle cell malignancy that lacks both significant pleomorphism and any line of differentiation other than fibroblastic.[5,20] This bone tumor typically develops in the soft tissue around the bones (eg, tendons, ligaments, fat, muscle) but can also arise as a primary or secondary bone tumor.[21] It usually occurs in older adults (but can affect any age), affects males more than females,[3] and involves the arms, legs, and jaw.[2,22]

On gross appearance, the tumor is a firm, white soft-tissue mass that shows extensive replacement of the cancellous and cortical bone.[23]

Histologically, fibrosarcoma of bone appears the same as soft-tissue sarcomas, generally showing atypical spindle-shaped fibroblasts in a herringbone pattern in a collagen background.[2,22] Because true histiocytic differentiation is lacking in these tumors, a thorough biopsy sampling is required to exclude other lines of differentiation.[9,20]

The preoperative image (left) reveals a huge fibrosarcarcoma in a 25-year-old patient. The histologic image (right) is from a fibrosarcoma in a different patient.

Images courtesy of (1) Adigun IA, Ogundipe KO, Bello JO. J Med Case Rep. 2009;3:7267. [Open access.] PMID: 19830159, PMCID: PMC2726520 (left), as well as (2) NCI/Dr Timothy Triche (right).

Slide 17

Workup

All patients should undergo a detailed history and physical examination. Note that a history of trauma does not rule out malignancy.[3,6] Obtain plain radiographs in two views of the affected area as an initial diagnostic study; the images can reveal the site, size, and shape of the bone tumor.[2,3,8]

The NCCN guidelines recommend referring all patients younger than 40 years with abnormal radiographs to an orthopedic oncologist for further workup that includes biopsy.[4,25] For patients aged 40 years and older, the recommended workup includes obtaining the following laboratory and radiologic studies[4,25]:

  • Routine laboratory tests, including a complete blood cell (CBC) count and levels of lactate dehydrogenase (LDH) and alkaline phosphatase (ALP)
  • Prostate-specific antigen (PSA) levels: Elevated levels may indicate osseous metastasis from prostate carcinoma in males
  • Serum protein electrophoresis (SPEP): In the initial evaluation of lytic bone lesions of unknown etiology, findings may determine the presence/absence of a plasma cell neoplasm[24]
  • Bone scan: This radionuclide imaging study can detect the presence of metastatic or multifocal disease
  • CT scan of the chest, abdomen, and pelvis: Imaging of the primary lesion identifies the tumor site and extent; CT scanning can also evaluate for metastasis to the lung and/or other organs.
  • Mammogram: This study may reveal the presence of breast carcinoma.
  • Other laboratory and/or imaging studies, as clinically indicated (eg, MRI [excellent for outlining bone tumors, evaluating brain and spinal cord, and staging of extremity and pelvic lesions][2,3]; positron emission tomography [PET] scanning [to assess for metastasis throughout the body][2])

Deep-sequencing genomic tests are increasingly a part of oncologic practice, although the NCCN guidelines do not include them.[25] Clinicians should consider discussing the options surrounding these studies with patients who present with locally advanced or metastatic chondrosarcoma, chordoma, or osteosarcoma. Deep sequencing may identify mutations, and thus may have therapeutic implications and may guide referral to clinical trials.[25]

Adapted image of a bone marrow biopsy procedure courtesy of Blausen Medical Communications, Inc, via Wikimedia Commons.

Slide 18

The ESMO guidelines recommend following up an abnormal radiograph with MRI of the entire compartment with the adjacent joints, but they only recommend CT scanning in the event of diagnostic challenges or uncertainty as well as for visual clarification of calcification, periosteal bone formation, or cortical destruction.[3,25]

Both the NCCN and ESMO guidelines agree that biopsy is required to confirm the diagnosis prior to any surgical procedure.[3,4,25]

This comparison bone scan shows the involved right shoulder (left image) relative to the uninvolved shoulder (right image) in an adolescent patient with osteosarcoma. (Same patient as in slide 6.)

Image courtesy of Medscape/Charles T Mehlman, DO, MPH.

Slide 19

Treatment

As discussed earlier, primary bone cancers are rare; therefore, when possible, a multidisciplinary team with expertise in the complex management of these tumors should treat affected patients.[3,4] The NCCN guidelines also recommend enrolling oncology patients in a clinical trial when available.[4]

Treatment modalities for bone sarcomas include one or more of the following[2-4,8]:

  • Surgical excision or wide resection (in selected cases, amputation)
  • Chemotherapy
  • Radiotherapy
  • Palliative radiotherapy and supportive care
  • Long-term/life-long surveillance and follow-up

The perioperative and follow-up images are from a middle-aged male patient with osteosarcoma.

Images A and B: Preoperative CT scans show the lesion within the L3 vertebra, right pedicle, and right lamina. The patient underwent total en bloc spondylectomy, through a single posterior approach.

Images C and D: The extracted specimens included the posterior element and the anterior portion of the vertebra.

Image E: A postoperative radiograph demonstrates the correct alignment of instrumentation. Titanium mesh filled with bone cement was used as anterior reconstruction, and a pedicle screw was applied in the posterior reconstruction.

Image F: A follow-up CT scan at 18 months demonstrates no relapse.

Images courtesy of Feng D, Yang X, Liu T, et al. World J Surg Oncol. 2013;11(1):89. [Open access.] PMID: 23597053, PMCID: PMC3642001.

Slide 20

Treatment: osteosarcoma

Prior to the advent of chemotherapy in the 1970s, the mainstay of osteosarcoma management was surgical resection (primarily by amputation).[9,26] However, although resection achieved good local control, the majority of patients subsequently developed recurrent disease that was metastatic. Thus, adjuvant systemic chemotherapy is critical for the treatment of patients with osteosarcoma.[9,26]

Neoadjuvant chemotherapy facilitates subsequent surgical removal by causing tumor shrinkage and also provides risk stratification. A good histopathologic response to neoadjuvant chemotherapy (>90% necrosis) in patients is predictive of survival regardless of the postoperative chemotherapy regimen administered.[4,26]

Currently, surgical intervention (limb sparing [preferred] or amputation) remains a critical treatment for patients with osteosarcoma.[3,25]

The images illustrate the results for a patient with osteosarcoma of the distal femur who was treated with preoperative chemotherapy and limb-sparing surgical resection.

Image A depicts preservation of the epiphysis of the distal femur by marginal resection.

Image B shows the remaining epiphysis, and image C shows the resected tumor.

Image D reveals successful healing of the implanted bone as seen on radiographs following insertion of an intramedullary nail and screws into the residual epiphysis and filling of the bone defect with bone cement (no barium).

Images courtesy of Xu M, Xu S, Yu X. World J Surg Oncol. 2014;12:341. [Open access.] PMID: 25391880, PMCID: PMC4234849.

Slide 21

First-line chemotherapy regimens for osteosarcoma include cisplatin/doxorubicin; MAP (high-dose methotrexate [MTX]/cisplatin/doxorubicin [Adriamycin]); doxorubicin/cisplatin/ifosfamide/high-dose MTX; and ifosfamide/cisplatin/epirubicin.[4]

Second-line chemotherapy regimens include, but are not limited to, the following[4]:

  • Gemcitabine and/or docetaxel
  • Cyclophosphamide and etoposide or topotecan
  • High-dose ifosfamide, with or without etoposide
  • Ifosfamide/carboplatin/etoposide
  • High-dose MTX/ifosfamide/etoposide
  • Sorafenib, with or without everolimus
  • Radium 223

These images illustrate osteosarcoma of the left distal femur in an adolescent male before (images A and B) and after (images C and D) receiving chemotherapy.

Image A: MRI of the tumor obtained before neoadjuvant chemotherapy; the arrows show the lesion in longest diameter.

Image B: Prechemotherapy histologic image of the tumor cells (H&E stain, at 40× magnification).

Image C: Postchemotherapy MRI of the same tumor. No tumor extension into the epiphysis is seen. A good response to therapy is indicated by the presence of extensive calcification and the significantly reduced lesion. The arrows show the sum of the longest diameter (≥30% reduction)

Image D: Postchemotherapy histology reveals significant tumor cell degeneration and necrosis (H&E stain, at 40× magnification).

Images courtesy of Xu M, Xu S, Yu X. World J Surg Oncol. 2014;12:341. [Open access.] PMID: 25391880, PMCID: PMC4234849.

Slide 22

Treatment: chondrosarcoma

The NCCN recommendations for treatment of chondrosarcomas include the following[4,25]:

  • Resectable low-grade and intracompartmental lesions: Wide or intralesional excision, with or without adjuvant therapy
  • Pelvic low-grade tumors, large tumors, and high-grade (II, III), clear cell, or extracompartmental lesions, if resectable: Wide excision (preferred)
  • Wide excision to achieve negative surgical margins by either limb-sparing surgery or amputation
  • Postoperative proton and/or photon beam radiation therapy for tumors in an unfavorable location (eg, skull, axial skeleton)
  • Consideration of radiation therapy for unresectable tumors

Because no established chemotherapy regimens exist for grade I-III chondrosarcomas, the NCCN guidelines recommend treatment of patients with dedifferentiated tumors to follow osteosarcoma guidelines, and treatment of patients with mesenchymal tumors to follow Ewing sarcoma guidelines.[4]

The preoperative images are from a patient with scapular chondrosarcoma. The left photograph shows an estimated 38 × 33 × 30 cm3 mass in the right scapula. The right images are CT scans of the same tumor.

Images courtesy of Chang F, Liu GY, Zhang Q, et al. World J Surg Oncol. 2014;12:196. [Open access.] PMID: 24976133, PMCID: PMC4090394.

Slide 23

These images are from the same patient with scapular chondrosarcoma seen in the previous slide, during (left) and following (right) limb-salvage surgery.

Images courtesy of Chang F, Liu GY, Zhang Q, et al. World J Surg Oncol. 2014;12:196. [Open access.] PMID: 24976133, PMCID: PMC4090394.

Slide 24

Treatment: Ewing sarcoma

The NCCN recommendations for treatment of Ewing sarcoma are as follows[4,25]:

  • Multiagent chemotherapy for at least 12 weeks, followed by surgery and adjuvant chemotherapy; consider longer duration of initial chemotherapy for patients with metastatic disease, based on treatment response
  • Localized disease, preferred chemotherapy regimen: VAC/IE (vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide)
  • Metastatic disease, preferred chemotherapy regimen: VAC (vincristine/doxorubicin/cyclophosphamide)
  • Restage following chemotherapy

The CT scans show a soft-tissue shadow on scout view (left) and a soft-tissue tumor (right) in a child with Ewing sarcoma of the right scapula.

Images courtesy of Waqar SH, Zahid MA. APSP J Case Rep. 2011;2(3):22. [Open access.] PMID: 22953289, PMCID: PMC3418025.

Slide 25

The photographs show the preoperative and postoperative images of the same child with right scapular Ewing sarcoma discussed in the previous slide. This patient also received postoperative chemotherapy with VAC and radiation therapy.

Images courtesy of Waqar SH, Zahid MA. APSP J Case Rep. 2011;2(3):22. [Open access.] PMID: 22953289, PMCID: PMC3418025.

Slide 26

Treatment: chordoma

NCCN recommendations for treatment of chordoma include the following[4,25]:

  • Conventional and chondroid tumors of the sacrum and mobile spine, if resectable: Wide excision with or without radiation therapy
  • Skull base conventional and chondroid tumors, if resectable: Intralesional excision with or without radiation therapy; consider re-resection for positive surgical margins; postoperative radiation therapy is useful for improved local control
  • Large extra-compartmental tumors or positive surgical margins after resection: Consideration of adjuvant radiation therapy
  • Unresectable tumors at any site: Radiation therapy

In general, chordomas are not sensitive to chemotherapy, with the exception of potentially dedifferentiated portions of high-grade differentiated tumors.[4] Potential chemotherapy agents to treat susceptible tumors include, but are not limited to, imatinib alone or with cisplatin or sirolimus; erlotinib; and sunitinib.[4]

The MRIs of the pelvis demonstrate a sacral chordoma (arrows).

Images courtesy of Wikimedia Commons/Harry Gouvas.

Slide 27

Treatment: fibrosarcoma

The NCCN and ESMO guidelines do not discuss management of fibrosarcomas.

The American Cancer Society (ACS) indicates that surgical resection with wide margins is the primary treatment for these tumors, with or without radiation therapy.[2] For unresectable or recurrent lesions, radiation therapy is used.[2]

Images courtesy of (1) Adigun IA, Ogundipe KO, Bello JO. J Med Case Rep. 2009;3:7267. [Open access.] PMID: 19830159, PMCID: PMC2726520 (left), as well as (2) NCI/Dr Timothy Triche (right).

Slide 28

Prognostic Factors, Prognosis, and Survival

As with many types of malignancies, factors that influence outcome in patients with bone sarcomas include the following[4,10,27]:

  • Primary tumor site, size, and grade
  • Presence and location of metastatic disease
  • Patient age and sex
  • Histologic response to chemotherapy
  • Surgical resectability and/or surgical margins

The site of the primary tumor is a significant prognostic factor for patients with localized disease.[4,10,27] For example, among extremity tumors, distal sites have a more favorable prognosis than proximal sites do, whereas axial skeleton primary tumors are associated with the greatest risk of progression and death, primarily related to the inability to achieve a complete surgical resection.[4,10,27] Larger tumors also have a worse prognosis than smaller tumors do.[4,10,27]

The postoperative images are from a patient with Ewing sarcoma who received neoadjuvant chemotherapy (vincristine/actinomycin-D/cyclophosphamide/doxorubicin alternating with ifosfamide/etoposide) and then underwent surgical resection with placement of an endoprosthesis.

The A-P radiographs of the left hip and thigh show the implant in situ following surgery (left image) and at 4 years follow-up (right image).

The center image is a postoperative photograph showing the resected proximal femur with tumor in situ.

Images courtesy of Rastogi S, Kumar A, Gupta H, Khan SA, Bakhshi S. Indian J Orthop. 2010;44(4):384-9. [Open access.] PMID: 20924478, PMCID: PMC2947724.

Slide 29

Patients with localized disease have better outcomes than do patients with overt metastatic disease; metastatic disease at presentation is the most significant adverse prognostic factor for the majority of bone sarcomas.[4,10,27] The prognosis for patients with metastatic disease appears to be determined largely by the site(s), the number of metastases, and the surgical resectability of the metastatic disease.[4,10,27]

Overall, about 66.7% of patients diagnosed with bone or joint cancer survive 5 years or more.[1] The highest percentage of deaths are among patients older than 55 years (median age at death: 59 years), as follows:

  • Age 75-84 years: 16.1%
  • Age 65-74 years: 14.4%
  • Age 55-64 years: 12.9%
  • Older than 84 years: 12.4%.

However, the second largest percentage of deaths after the 75-84 year age group is among those aged 20-34 years (15.1%).[1]

The lowest percentage of deaths occurs among those aged 35-44 years (5.9%).[1]

Image courtesy of the NCI/SEER Program.[1]

< Previous Next >
  • Google+
  • LinkedIn
EXIT FULLSCREEN

.