. Conventional Chondrosarcoma, Central or Medullary. PORTNotes. In: OrthopaedicsOne - The Orthopaedic Knowledge Network. Created Feb 16, 2009 16:34. Last modified Nov 19, 2011 19:09 ver.7. Retrieved 2018-12-14, from https://www.orthopaedicsone.com/x/rwAjAQ.
DEFINITION AND PATHOGENESIS
- Primarily arising de novo from bone within the IM canal, either low (grade I) or intermediate (grade II)
- Distinction between enchondroma and low grade IM lesions radiographically and grossly impossible, and difficult with frozen section, so preoperative planning is imperative for appropriate tx
- 2nd most common sarcoma of bone
- Rarely seen in children, mean age 46 (5-82)
- Mean age of 55 (28-93) in hand/foot lesions
- 11-22% of all primary malignant bone tumors (1/2 as common as osteosarcoma)
- 31% arise in the pelvis, 21% in the femur, ?6% in the spine (T>L>C)(usually stage IB lesions)
- Local swelling, pain (81.4%), mass (33.1%), and tenderness; may grow very slowly
- Pathological fx (8.1%)(15% in spinal lesions)
- M:F = 1.3:1
- ± adhesive capsulitis in proximal humeral location
- Absence of pain does not exlude chondrosarcoma
- Metaphyseal, diaphyseal, rarely epiphyseal
- Punctate, flocculent, or rings-and-arcs and popcorn-like calcifications (ossification around cartilage lobules)
- Regions of the lesion don't retain geographic borders, esp in higher grade lesions
- Lucencies represent replacement of normal bone by uncalcified cartilage (and without calcifications represent areas of higher grade)
- Lesion may be "bubbly" in appearance
- Pathologic fx or stress fx can occur (more commonly in higher grade tumors)
- Erosion of cortex with breakthrough and a soft tissue mass heralds sarcoma and Grade II status
- Deep endosteal scalloping (>2/3 of cortical thIickness)
- 9/12 hand/foot lesions have at least one of the following:
- Cortical destruction (8/12)
- Soft tissue extension (7/12)
- Periosteal reaction (4/12)
- CT for cortical extent and matrix delineation, and MRI for medullary extent and soft tissue mass or extension
- T2-weighted images: tumor has bright signal intensity, calcifications have low signal intensity on all se-quences, contrast enhancement in a ring and arc septal pattern; heterogeneity of signal intensity correlates with higher grade, more cellular lesions
- Bone scan reveals ? uptake, esp along the periphery of the lesion
- Angiography useful in large pelvic lesions, or thigh lesions for preoperative planning
- IVP helpful in large pelvic lesions (ureteral stint placement can be helpful prior to resection to palpate for location)
- When occurring in the sternum, nearly all are malignant
- When >6-10cm, lesions must be considered most likely malignant
- Extension through articular cartilage and through ligaments may occur
- Soft tissue mass is often surrounded by periosteal new bone or fibrous pseudocapsule
HISTOLOGIC AND MOLECULAR FEATURES
- If there is malignant osteoid, it is an osteosarcoma
- Histologic grades "½"-I (60.9%) and II (35.3%), recently "grade 1/2" has been coined; rarely grade III (3.2%)
- (Older pts tend to have higher grade tumors)
- ? cellularity and cytological atypia most important in determining grade
- Hyaline cartilage (may be myxoid) with atypical cells, varibly sized nuclei, and ? cellularity and clumping of cells (cloning), mitotic figures (8%)
- Myxoid matrix (87%)
- Trabecular trapping (67%)
- Collagenase-3 (MMP-13) present in a reported 100% of chondrosarcomas and 25% of benign cartilage tumors by immunohistochemistry
- von Hippel-Lindau protein significantly reduced in chondrosarcoma tissues
- Positively correlated with Bax expression
- Positively correlated with apoptosis index in chondrosarcoma
- (Reduced expression with decreased apoptosis)
- (Not independently predictive of survival)
- von Hippel-Lindau protein a positive regulator of p53
- (von Hippel-Lindau protein loss of function may lead to malignancy)
- Impaired von Hippel-Lindau protein levels have increased concentrations of HIF-? and HIF target gene products
- HIF-? plays a role in evasion of apoptosis by chondrosarcoma cells
- Associated with elevated levels of anti-apoptotic protein Bcl-xL
- HIF-? plays a role in evasion of apoptosis by chondrosarcoma cells
- Endothelin-1 (potent vasoconstrictor) expression
- Increased migration and expression of MMP-13
- Reduced by pretreatment with inhibitors:
- Focal adhesion kinase
- Phosphatidylinositol 3-kinase
- Mammalian target of rapamycin (mTOR)
- NF-?B inhibitor
- I?B protease inhibitor
- Reduced by pretreatment with inhibitors:
- Endothelin-1 tx induced phosphorylation of:
- Endothelin-1 tx resulted in increased activated FAK/PI3K/AKT/mTOR
- In turn activated IKK?/? and NF-?B
- Resulting in crased MMP-13 expression and migration in chondrosarcoma cells
- In turn activated IKK?/? and NF-?B
- Increased migration and expression of MMP-13
DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS
- Enchondroma, atypical enchondroma
- Chondroblastic osteosarcoma (or other histiocytic types)
- Sheets of spindle cells, chondroid lobules and lace-like osteoid
- IM infarcts, osteonecrosis
- Intraosseous (ossifying) lipoma
- Metastatic disease or multiple myeloma
DISEASE COURSE AND TREATMENT
- Wide resection in ³ grade II lesions (contaminated margins will allow local recurrence, low oxygen tension in hematoma will sustain malignant cartilage growth in surrounding soft tissue)
- Uncontaminated, clear margins the goal in pelvic resections
- Ray resection (or limited amputation in phalangeal location) in hand/foot lesions
- Biopsy the soft tissue mass (to R/O a higher grade lesion), otherwise low grade lesions best treated without bx, but with careful preoperative planning because of characteristic radiographical findings and problems with misdiagnoses associated with sampling errors
- Cryosurgery after curettage and burring for low grade ("1/2" to 1) lesions (without soft tissue mass)
- Metastases occur in <15% of low grade lesions and 15-50% of intermediate (grade II) lesions (tumor grade most important prognostic factor)
- Poorer prognosis in axial lesions (including pelvic location), and incompletely curetted or resected lesions
- Aggressively resecting pelvic chondrosarcomas results in long term survival (the outcome is determined by the adequacy of the resection)
- 94% 1 yr, 82% 5 yr, 80% 10 yr, 77% 15 yr survival for pelvic chondrosarcomas
- Re-resection of pelvic LR may result in cure
- 5-year survival of pts with condrosarcoma of the spine is 55%, median survival 6 yrs
- Relatively avascular tumor allows mechanical transplantabiltiy from one site to another (esp with < wide resec-tions)
- Recurrences usually herald a stepup in grade and ? metastases (and possibly under tx in the first place)(may not occur for >10 years after initial tx)
- Progression may occur via intravenous extension or to adjacent vital structures
- Chemotherapy or XRT not helpful in controlling local disease or metastases
- XRT should be considered in vertebral lesions when surgical ablation is not obtainable
- Fluoroquinolone toxic to immature chondrocytes and their use in chondrosarcoma under investigation (induces oxidative metabolism?impairment of proteoglycan and procollagen synthesis; interacts with topoisomerase II?? inhibits DNA replication?DNA strand breaks and apoptosis)
- ? incidence of LR and metastases when p53 overexpression or alteration is present (38% of conventional chondrosarcomas), mitoses, a myxoid tumor matrix, necrosis, high-grade tumor, size >100cc, and a ploidic abnormality (aneuploidy/high mean DNA index)
- MIB-1 expression associated with recurrence and death (more predictive than histologic grade)
Low ratio of mRNA expression of matrix metalloproteinase-1 to the tissue inhibitor of metalloproteinase-1 low histological grade, and F gender predictors of better prognosis
- INTRACORTICAL CHONDROSARCOMA
- Lucent lesion within the cortex
- Intermediate grade chondrosarcoma which requires en bloc resection
- MULTICENTRIC CHONDROSARCOMAS
- May be monomelic (± skip lesions) or disseminated
- Can be synchronous, metachronous, occasionally with Ollier's disease
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