Chondrosarcoma

Overview

Definition

Chondrosarcoma is a malignant bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumor Tumor Inflammation characterized by the production of a cartilaginous matrix.

Epidemiology

• Primary malignant bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumors:  
  • 6th most common neoplasm in children
  • 3rd most common neoplasm in adolescents and young adults
  • Approximately 3,000 primary malignant bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumors are diagnosed annually in the United States.
  • Approximately 1,500 deaths result from primary malignant bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumors annually.
• Chondrosarcoma:
  • 20%–25% of primary bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types malignancies
  • Highest incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in adults over 50
  • Pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy and long bones Long bones Length greater than width. Bones: Structure and Types are most commonly affected.

Etiology

• Can arise:
  • De novo from normal bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
  • Via malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology of enchondroma/osteochondroma
• Myc amplification, multiple mutations, and chromosomal structural anomalies have been implicated in pathogenesis.
• Predisposing inherited disorders:
  • Ollier disease 
  • Maffucci syndrome

Pathophysiology

• Mutations and chromosomal abnormalities play a major role in pathogenesis.
• Normally, chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology within a growth plate undergo hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation, differentiation, and apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage to allow for the ingrowth of vessels and osteoblasts Osteoblasts Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. Bones: Development and Ossification (allowing for bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types formation):
  • This process becomes dysregulated in chondrosarcoma formation.
• There are many histological subtypes:
  • Most common subtype is conventional ( hyaline cartilage Hyaline cartilage A type of cartilage characterized by a homogeneous amorphous matrix containing predominantly type II collagen and ground substance. Hyaline cartilage is found in articular cartilage; costal cartilage; laryngeal cartilages; and the nasal septum. Cartilage: Histology producing) chondrosarcoma, accounting for 80%–90% of these tumors.
• Morphology:
  • Translucent, lobular, cartilaginous cut surface with cystic Cystic Fibrocystic Change/mucoid areas
  • Abundant cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology matrix production
• Tumor Tumor Inflammation’s aggressiveness determines histological grade:
  • Tumors will be graded 1–4.

Clinical Presentation

• Longstanding dull, achy pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways with swelling Swelling Inflammation and redness Redness Inflammation
• Progressive increase in the size of the mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
• Neurological symptoms if the tumor Tumor Inflammation is close to a neurovascular bundle:
  • Lumbosacral plexus in the pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy
  • Cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. The 12 Cranial Nerves: Overview and Functions in the base of the skull Base of the skull The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface. Skull: Anatomy
• Limitation of range of motion Range of motion The distance and direction to which a bone joint can be extended. Range of motion is a function of the condition of the joints, muscles, and connective tissues involved. Joint flexibility can be improved through appropriate muscle strength exercises. Examination of the Upper Limbs (if close to the joint)
• Pathologic fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures
• Most will grow slowly and have low metastatic potential.
• When spreading occurs, the spread is primarily to the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy.

Diagnosis

History and physical exam

• Vague pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways/ swelling Swelling Inflammation
  • Gradually increasing
  • May be worse at night
• Neurologic symptoms (if nerve compression Nerve Compression Brachial Plexus Injuries is present)
• History of relevant congenital Congenital Chorioretinitis diseases
• Palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast

Imaging

• X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • Calcification in the medullary cavity Medullary Cavity Ewing Sarcoma (popcorn calcification)
  • Radiolucency
  • Usually, no pronounced periosteal reaction
• MRI:
  • Test of choice for primary tumor Tumor Inflammation evaluation
  • Evaluates the extent of the tumor Tumor Inflammation, marrow, and soft tissue Soft Tissue Soft Tissue Abscess involvement
• CT and bone scan Bone Scan Osteosarcoma:
  • For primary tumor Tumor Inflammation and distant metastatic disease evaluation
  • May show matrix mineralization Matrix mineralization Bones: Development and Ossification, endosteal scalloping, and/or cortical breach

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

• Definitive diagnosis
• Should be taken from the most aggressive-appearing portion of a lesion

Management

Surgery

• Offers the only chance of cure
• Wide surgical excision is the mainstay of treatment.
• In some central low-grade lesions, the intralesional curettage Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Benign Bone Tumors with local phenolization or cryotherapy followed by bone grafting Bone Grafting Benign Bone Tumors of the cavity can be performed.
• For peripheral lesions arising in osteochondromas Osteochondromas Benign Bone Tumors, complete removal of cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology cap is recommended.

Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma

• Chondrosarcomas are relatively radioresistant.
• Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma can be used for palliation.
• For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with incomplete resection or when resection is not feasible

Chemotherapy Chemotherapy Osteosarcoma

• Chondrosarcomas are generally chemoresistant.
• Not used as adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination or neoadjuvant treatment
• Role in the treatment of metastatic disease is also limited.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Determined by grade
• 83% 5-year survival rate for grade 1 tumors
  • Falls to 53% for grade 2 and grade 3 tumors

Differential Diagnosis

• Ewing sarcoma Ewing Sarcoma Ewing sarcoma (ES) is a primary bone malignancy derived from primitive round cells affecting primarily children and teenagers. Ewing sarcoma commonly presents with a painful mass, swelling, and pathologic bone fractures. Ewing Sarcoma: primary bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types malignancy Malignancy Hemothorax composed of poorly differentiated cells that most commonly affects adolescents. This malignancy Malignancy Hemothorax presents with localized pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and swelling Swelling Inflammation. Diagnosis is established with imaging and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management is based on chemotherapy Chemotherapy Osteosarcoma and surgical resection.
• Osteosarcoma Osteosarcoma Osteosarcoma is a primary malignant tumor of the bone characterized by the production of osteoid or immature bone by the tumor cells. The disease is most common in children and young adults and most frequently affects growth plates of the long bones, although it can involve any bone. Osteosarcoma: a malignant bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumor Tumor Inflammation characterized by the production of immature bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types. Most common in children and young adults. This tumor Tumor Inflammation presents with pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, swelling Swelling Inflammation, palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, and pathologic fractures. Diagnosis is suspected on imaging and confirmed with tissue biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management includes surgical resection and systemic chemotherapy Chemotherapy Osteosarcoma.
• Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types metastases: metastatic bone lesions Bone Lesions Multiple Myeloma from primary cancers arising at other sites, most commonly prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. , breast, and lung. These metastases present with bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, pathologic fractures, and constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Diagnosis is made based on clinical history and imaging. Treatment includes systemic chemotherapy Chemotherapy Osteosarcoma as well as supportive measures aimed at minimizing pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and pathologic fractures.
• Benign Benign Fibroadenoma bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumors: more common than malignant bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumors. These types of tumors include enchondroma, osteochondroma, nonossifying fibroma, chondroblastoma, osteoid osteoma Osteoid Osteoma Benign Bone Tumors, osteoblastoma Osteoblastoma A benign, painful, tumor of bone characterized by the formation of osteoid tissue, primitive bone and calcified tissue. It occurs frequently in the spine of young persons. Benign Bone Tumors, periosteal chondroma, giant cell tumor Tumor Inflammation, and chondromyxoid fibroma. Many benign Benign Fibroadenoma bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types tumors, however, may present with the risk of malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology. 
• Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis: bone infection Bone infection Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by staphylococcus aureus. Osteomyelitis most commonly due to pyogenic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology in the setting of orthopedic injury or a chronic nonhealing wound that erodes into the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types. Presents with localized pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, signs of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation/infection, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever; can progress to sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock and limb loss. Treatment is aggressive antibiotic therapy with or without surgical debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome.
• Orthopedic injury: strains, sprain, growing pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and fractures are the precipitating events that bring bony tumors to clinical attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment. However, a more innocent injury or process may be to blame when considering the possibility of a bony neoplasm. Orthopedic injury is characterized by localized pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation/ swelling Swelling Inflammation. Diagnosis is usually made clinically, and management is supportive.