Bone & joints
Osteogenic tumors
Malignant
Low grade (central) osteosarcoma
Author: Borislav A. Alexiev, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 24 November 2020
Last staff update: 8 January 2021
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: low grade central osteosarcoma[title]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Alexiev BA. Low grade (central) osteosarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/boneLGcentralosteo.html. Accessed December 18th, 2024.
Definition / general
- Low grade central osteosarcoma (LGCOS) is a low grade malignant bone forming neoplasm that originates within the medullary cavity and consists of fibroblastic tumor cells with low grade nuclear atypia and well formed neoplastic bony trabeculae
Essential features
- Predominantly fibroblastic osteosarcoma with mild nuclear atypia and well formed neoplastic bony trabeculae
- Intramedullary location
- MDM2 amplification
- Good prognosis when widely resected
Terminology
- Well differentiated intramedullary osteosarcoma
ICD coding
- ICD-O: 9187/3 - Low grade central osteosarcoma
- ICD-11: 2B51.Z & XH7N84 - Osteosarcoma of bone and articular cartilage of unspecified sites & low grade central osteosarcoma
Epidemiology
- Accounts for only 1 - 2% of all osteosarcomas (Sarcoma 2012;2012:764796)
- Equal gender distribution (Sarcoma 2012;2012:764796, Cancer 1990;65:1418)
- Majority of cases occur in the second and third decades (Cancer 1990;65:1418)
Sites
- Most often affects the metaphysis of long bones, predominantly the femur and tibia (Sarcoma 2012;2012:764796)
- Small tubular bones, jaw bones and ribs are rarely involved (Cancer 1993;72:719, Am J Surg Pathol 2010;34:1647, Oral Oncol 1999;35:530, Skeletal Radiol 2005;34:490, Clin Orthop Relat Res 2008;466:1318)
Pathophysiology
- Majority of cases are driven by amplification of 12q13-q15 involving MDM2 and CDK4 (see Molecular / cytogenetics description)
Etiology
- Unknown
Clinical features
- Slow growing mass (Int J Clin Oncol 2014;19:731)
- Primary symptom is pain / swelling of longer duration than conventional osteosarcoma (Clin Orthop Relat Res 1996;322:198, Mod Pathol 2010;23:1279)
- There are reports of multifocal tumors located in 2 distinct skeletal sites (Skeletal Radiol 2016;45:997)
Diagnosis
- Tissue sampling is the gold standard for a definitive diagnosis
- When the radiologic diagnosis suggests a nontypical osseous lesion, clinicians should exercise caution during follow up of the lesion after the initial biopsy results in a benign diagnosis (Int J Clin Oncol 2014;19:731)
- Open biopsy is better to obtain additional samples (Int J Clin Oncol 2014;19:731)
- Lack of MDM2 amplification cannot exclude the diagnosis
- Any difficult or nondiagnostic biopsies of solitary bone lesions should be referred to specialist tumor units for a second opinion (Sarcoma 2012;2012:764796)
Radiology description
- Usually involves the metaphysis and diaphysis of long bones
- Typically presents as large intramedullary lytic or sclerotic lesion with coarse trabeculation, often extending to the articular surface (Skeletal Radiol 2004;33:373, World J Orthop 2013;4:327)
- Always strongly enhanced by gadolinium in MRI (Arch Orthop Trauma Surg 2008;128:11)
- Cortical disruption or soft tissue extension may be present (Skeletal Radiol 2004;33:373)
Radiology images
Contributed by Borislav A. Alexiev, M.D.
MRI of tibia mass
Prognostic factors
- Good prognosis (Cancer 1990;65:1418, Clin Orthop Relat Res 1996;322:198, Sarcoma 2012;2012:764796)
- Limited metastatic potential (Cancer 1977;40:1337, Arch Orthop Trauma Surg 2008;128:11)
- 90% overall survivorship at 5 years (Sarcoma 2012;2012:764796)
- Presence of dedifferentiation confers a worse prognosis
Case reports
- 19 year old woman with a lytic lesion in her left proximal humerus (Onco Targets Ther 2017;10:5165)
- 32 year old man with a lytic lesion of the distal femur (World J Orthop 2013;4:327)
- 33 year old man with a gradually growing mass in his chest wall (Case Rep Pathol 2013;2013:798435)
- 46 year old woman with an ill defined densely sclerotic lesion of the proximal tibia and 53 year old woman with a purely sclerotic lesion of the proximal tibia (Mod Pathol 2004;17:288)
Treatment
- Most important factor in adequate treatment is an accurate diagnosis
- Should be treated by wide excision, even after intralesional excision, because intralesional excision alone leads to a poorer prognosis (Cancer 1993;71:338, Int J Clin Oncol 2014;19:731)
- Dedifferentiated LGCOS patients are treated with chemotherapy largely according to regimens for conventional osteosarcoma (Bone Joint J 2019;101-B:745)
Gross description
- Most often affects the metaphysis of a long bone
- Usually poorly circumscribed, a feature reflecting infiltrative growth
- Tumor sometimes has a well defined margin
- White rubbery fibrous cut surface with gritty calcifications, located in the medullary cavity
- Cortical destruction and soft tissue infiltration may be present
- References: Clin Sarcoma Res 2018;8:16, Pathol Int 2003;53:115
Gross images
Contributed by Borislav A. Alexiev, M.D.
Bone mass
Frozen section description
- Cellular fascicles of spindle cells with mild nuclear atypia admixed with neoplastic bone component
Microscopic (histologic) description
- Mildly to moderately cellular fascicles of spindle (fibroblast-like) cells with mild nuclear atypia embedded in a fibrosclerotic stroma
- Neoplastic bone component which typically consists of irregular anastomosing long and thick bony trabeculae, often in parallel arrangement
- Bone is woven or lamellar
- Pagetoid bone may be present (Mod Pathol 2004;17:288)
- Invasive growth pattern (infiltration of the medullary spaces with encasement of preexisting trabeculae)
- Cortical destruction and soft tissue infiltration may be present
- Low mitotic activity (Cancer 1977;40:1337)
- Cartilage formation may be focally present (Cancer 1990;65:1418)
- Some tumors focally lack bone matrix
- Can progress high grade sarcoma (dedifferentiation) (Hum Pathol 2000;31:615)
- High grade areas often show high grade osteosarcoma histology
- Variant morphology
- Fibrous dysplasia-like pattern of bone deposition (Cancer 1990;65:1418, Cancer 1993;71:338, Mod Pathol 2010;23:1279)
- Extensive fibrous zone resembling desmoplastic fibroma (Cancer 1990;65:1418, Cancer 1993;71:338, Mod Pathol 2010;23:1279)
- Prominent cartilage cap mimicking osteochondroma (Mod Pathol 2010;23:1279)
Microscopic (histologic) images
Contributed by Borislav A. Alexiev, M.D.
Cortical destruction
Well formed neoplastic bone trabeculae
Fascicles of spindle cells
Lack of bone matrix
Mild nuclear atypia
Positive stains
Negative stains
- S100, AE1 / AE3, CD34, ERG and h-caldesmon
Electron microscopy description
- Predominant cells are fibroblasts with well developed rough endoplasmic reticulum
- Few osteoblasts and myofibroblasts
- Transition cells between fibroblasts and osteoblasts
- Presence of osteoid matrix
- Reference: Ultrastruct Pathol 2006;30:293
Molecular / cytogenetics description
- Chromosome 12q13-15 amplification containing CDK4 and MDM2 genes (Mod Pathol 1998;11:421, Am J Surg Pathol 2018;42:1143, Mod Pathol 2011;24:624)
- Amplification of 6p12-p21 and gains of 8q21-q24, 10p15, 12q13-q15 and 16q23-q24 (Anticancer Res 2012;32:5429)
- Deletion of the long arm of chromosome 13 (q12q32), associated with loss of the RB1 tumor suppressor gene (Clin Sarcoma Res 2018;8:16)
- GNAS mutations are not detected (unlike fibrous dysplasia) (Mod Pathol 2015;28:1336)
Molecular / cytogenetics images
Contributed by Madina Sukhanova, Ph.D.
MDM2 FISH
Sample pathology report
- Bone, left distal tibia, excision:
- Low grade osteosarcoma (see comment)
- Comment: Magnetic resonance imaging shows an enhancing lesion involving the distal tibial metadiaphysis with marked cortical scalloping. The lesion extends to the epiphysis. Hematoxylin eosin stained tissue sections show moderately cellular fascicles of spindle cells with mild nuclear atypia embedded in a fibrosclerotic stroma admixed with a neoplastic bone component, which consists of irregular anastomosing bony trabeculae. Permeation of host bone (infiltration of the medullary spaces with encasement of preexisting trabeculae) is present. Mitoses are extremely rare (1/10 high power fields). FISH shows MDM2 amplification in tumor cells. The findings support the diagnosis of low grade osteosarcoma. Low grade osteosarcoma has a good prognosis, when widely resected, with metastatic rate of < 5%.
Differential diagnosis
- Fibrous dysplasia:
- Irregular, curvilinear trabeculae of woven bone, which is arranged in a pattern commonly referred to as resembling Chinese characters (Arch Pathol Lab Med 2013;137:134)
- Conspicuous absence of osteoblastic rimming (Arch Pathol Lab Med 2013;137:134)
- GNAS activating mutations in 50 - 70% (Hum Pathol 2012;43:1234, Appl Immunohistochem Mol Morphol 2016;24:660)
- No MDM2 amplification
- Desmoplastic fibroma:
- Fascicles of bland spindle cells in a collagenous matrix
- Nuclear beta catenin expression may be present (Clin Sarcoma Res 2018;8:16)
- There are reports of CTNNB1 mutations (Clin Sarcoma Res 2018;8:16, Head Neck Pathol 2014;8:291)
- No MDM2 amplification
- Low grade fibrosarcoma:
- Proliferation of bundles of uniform fibroblastic spindle shaped cells with minimal cellular atypia, mixed with abundant intercellular collagenization (Pathol Int 2003;53:115)
- Absence of neoplastic bone component (Pathol Int 2003;53:115)
- No MDM2 amplification
Board review style question #1
A 27 year old man presents with a left proximal femur mass. Hematoxylin eosin stained tissue sections show moderately cellular fascicles of spindle cells with mild nuclear atypia embedded in a fibrosclerotic stroma admixed with a neoplastic bone component. Infiltration of the medullary spaces with encasement of preexisting trabeculae and cortical destruction is present. Mitoses are extremely rare (1/10 high power fields). Immunohistochemical stain for MDM2 is positive in tumor cells while all of the following are negative: S100, AE1 / AE3, CD34, ERG and h-caldesmon. FISH studies demonstrate amplification of MDM2 (12q15).
Which of the following is most likely the correct diagnosis?
- Low grade osteosarcoma
- Ossifying fibromyxoid tumor
- Adamantinoma
- Fibrous dysplasia
- Desmoplastic fibroma
Board review style answer #1
Board review style question #2
Which of the following is true about low grade central osteosarcoma?
- Most often affects jaw bones
- Has a good prognosis with a metastatic rate of < 5%
- Is the most common primary sarcoma of the skeleton
- GNAS mutation is common
- Presence of cortical disruption and soft tissue infiltration rules out the diagnosis
Board review style answer #2
B. Has a good prognosis with a metastatic rate of < 5%
Comment Here
Reference: Low grade intraosseous (central) osteosarcoma
Comment Here
Reference: Low grade intraosseous (central) osteosarcoma
