BONE CANCERS

 WHAT DOES A LONG BONE CONSIST OF?

diaphysis (the main shaft of the bone),

two epiphyses (the knoblike portions at either end of the bone),

the cartilage cap (covers the articular surface), and the periosteum (the hard, dense covering of the bone)

WHAT OCCURS IN THE GROWTH (EPIPHYSEAL) PLATE? 

• is the area in long bones where rapid cell proliferation and remodeling activity occur

• BC THEY POSSESS LARGE GROWTH PLATES, THE DISTAL FEMUR & PROXIMAL TIBIA are the two most common locations for bone tumors 

 WHERE DO NEOPLASMS OCCUR?

• In areas of rapid growth 

 WHAT IS THE MOST COMMON SITE OF A PRIMARY BONE SARCOMA?

• Near the growth plate

WHERE ARE OSTEOSARCOMAS MOST COMMONLY FOUND?

• found in the distal femur, followed by the proximal tibia and proximal humerus

 WHERE ARE CHONDROSARCOMAS MOST COMMONLY FOUND?

• Typically found in pelvis and femur

• Can involve the shoulder girdle and proximal humerus

Where are Fibrosarcomas (malignant fibrous histiocytoma- MFHs) and Giant cell tumor of bone (GCTBs) commonly found? 

• Typically arise in the metaphysis and epiphysis of long bones, including the distal femur, proximal tibia, and distal radius

 WHERE ARE EWING SARCOMAS COMMONLY FOUND? 

• Most frequently seen in the appendicular skeleton, with most tumors developing in the pelvis and femur

•  Can occur in any part of the bone but is most often seen in the diaphysis

 WHAT ARE THE MOST COMMON SITES OF METASTATIC BONE DISEASE?

• Most often involves the spine, pelvis, femur, and humerus

The most common cancers to metastasize to bone are

advanced diseases of the:

• lung, breast, and prostate

WHAT IS THE MOST COMMON OF ALL BONE TUMORS (35%)?

• Osteosarcoma

• Less common in adults but more prevalent in children 

WHO DO OSTEOSARCOMAS AFFECT THE MOST?

• Most common osseous malignant bone tumor in children

• Children and young adults between 10 and 30 years are most affected, more prevalent in young males, avg age 18 in males and 16 in females

WHAT IS THE MOST COMMON PRIMARY BONE TUMOR IN ADULTS (40%)?

• Chondrosarcoma, rare in children 

WHERE CAN FIBROSARCOMAS OCCUR? 

• May occur in bone or soft tissue (MFH group)

WHICH GROUP DOES FIBROSARCOMA AFFECT THE MOST?

• Diagnosed between the ages of 30 - 80 years, majority in 4th decade

•  Incidence slightly higher in males

WHICH GROUP DOES EWING SARCOMA AFFECT THE MOST?

• Affects ages 5 mos-60 years, peak incidence in 10-20 years of age, rare in those < 5 years old

• Unusual in Asian and African children

• More predominant in males than females

 WHAT IS MULTIPLE MYELOMA?

• Malignant disease of plasma cells, arises in B-cell lymphocytes of bone marrow

• Abnormal resorption of bone causes painful osseous lesions

WHICH GROUP DOES MULTIPLE MYELOMA AFFECT THE MOST?

• Mostly seen in middle-aged and older adults, with a peak incidence in the sixth decade

• More common in men

WHICH BONE CANCER IS TWICE AS COMMON IN BLACK PEOPLE?

• Multiple Myeloma 

WHAT IS GIANT CELL TUMOR OF BONE?

• Typically benign, but joint mobility can be limited as it grows

• Affects adults 20-40 years of age, common incidence in males and females

• Arises on metaphysis or epiphysis of long bones

WHAT IS METASTATIC BONE?

•  Accounts for most malignant bone lesions

• Occurs most often in spine, pelvis, and ribs followed by skull, humerus, and femur

 WHAT IS THE ETIOLOGY OF OSTEOSARCOMAS?

•  Cause unknown

• Genetics- RB1 and TP53

•  Li-Fraumeni syndrome

•  Heavy birth weight

•  Above avg. height

•  History of radiation*

WHAT IS THE ETIOLOGY OF OSTEOSARCOMAS?

• Cause unknown

•  Genetic alterations and molecular occurrences involving translocation (TET) anderythroblast transformation- specific (ETS) genes, the translocation leads to gene fusion which opens the door for cancer development

WHAT IS THE MOST COMMON SYMPTOM OF A BONE TUMOR?

• Pain that occurs with or without a mass

WHAT IS THE CLINICAL PRESENTATION OF AN OSTEOSARCOMA?

• usually nonspecific pain and swelling that becomes progressively worse over several months

What is the clinical presentations of chondrosarcomas, fibrosarcomas, and GCTs?

• symptoms similar to osteosarcomas, but the duration of the symptoms may be longer

WHAT DOES PAIN CORRELATE WITH IN BONE TUMORS?

• with degree of histologic aggressiveness of disease, rapid worsening of symptoms may indicate the histologic grade or cell type

WHICH BONE CANCER IS PATHOLOGIC FRACTURES COMMON, MAY SEE NEUROLOGIC ABNORMALITIES IN VERTEBRAL LESIONS, DECREASED ROM, AND MUSCULAR ATROPHY?

• Fibrosarcoma 

WHAT IS THE CLINICAL PRESENTATION OF AN EWING SARCOMA?

• pain and swelling in the affected area, often awakening them during sleep

• May also feel stiffness over the course of several weeks or months

• many patients will have asymptomatic metastatic disease at the time of diagnosis

WHAT IS THE CLINICAL PRESENTATION OF MULTIPLE MYELOMA?

• bone loss, caused by a disruption in the process of bone formation and resorption, which results in painful bony lesions

• may also have pathologic fractures and hypercalcemia, which sets this disease apart from the other primary bone tumors

WHAT IS THE CLINICAL PRESENTATION OF METASTATIC BONE DISEASE? 

• increasing pain that develops gradually over a few weeks or months

• Inflammation or the actual tumor causes the pain

•  The pain is often difficult to localize and becomes progressively worse

•  Left untreated, symptoms can be debilitating, which could result in pathologic fracture

WHAT ARE THE STEPS OF DIAGNOSING BONE TUMORS?

• H&P

•  Imaging of primary tumor site

•  MRI or CT with contrast

•  Chest/abdomen/pelvis CT with contrast

•  PET/CT scan of base of skull through mid-femur

•  Bone scan for rare cases or when

• PET/CT is inconclusive

•  Biopsy for confirmation of diagnosis

 TRUE OR FALSE? Early and/or incidental detection is rare

TRUE

TRUE OR FALSE? H&P to determine duration of symptoms, chronic symptoms may indicate a benign condition whereas acute may indicate malignancy. 

TRUE

TRUE OR FALSE? PET/MRI is more useful than PET/CT in the evaluation of primary bone tumors

TRUE

WHAT IS THE MOST IMPORTANT STEP IN CONFIRMATION OF A PATHOLOGIC DIAGNOSIS?

BIOPSY

WHAT IS THE PREFERRED BIOPSY METHOD BUT WHAT IS ITS DISADVANTAGES?

• core needle open biopsy is the preferred method, One of the disadvantages of open biopsy is the risk for tumor cell seeding

WHAT IS THE FIRST DIAGNOSTIC IMAGE OBTAINED AND WHY?

• A radiograph is first diagnostic image obtained; A useful practice is to rule out a pathologic fracture and determine whether surgical intervention is necessary

WHAT IS A SIGNIFICANT PROGNOSTIC FACTOR OF BONE CANCERS?

• GRADE, Classified as either low (G1) or high (G2) and is nearly synonymous with early (I and II) or late (IIB and III) stage

• Due to low incidence, sarcomas are difficult to stage

 WHAT IS THE SPREAD PATTERN OF LOW GRADE BONE TUMORS?

• do not readily metastasize, which makes them easier to control

WHAT IS THE SPREAD PATTERN OF SARCOMAS (ESPECIALLY HIGH GRADE)? 

• metastasize through the blood to the lungs

TRUE OR FALSE? Lymphatic spread is not of great concern unless tumor is in trunk of the body

TRUE

TRUE OR FALSE? Osteosarcomas demonstrate skip metastases in same bone or opposing side of the joint space

TRUE

 WHAT IS THE MOST IMPORTANT PROGNOSTIC INDICATOR FOR OSTEOSARCOMAS?

• the presence or absence of metastases at diagnosis (approx. 15-20% present with distant mets)

WHAT DOES THE PROGNOSIS OF CHONDROSARCOMA DEPEND ON?

• histologic grade and location (if located peripherally, it is more surgically accessible)

 WHAT ARE THE PROGNOSTIC INDICATORS FOR FIBROSARCOMA? 

• histologic grade, location in the bone (medullary or periosteal), and whether the lesions arise de novo (anew) or are secondary to a preexisting bony condition

WHAT ARE THE PROGNOSTIC INDICATORS OF MULTIPLE MYELOMA?

• patients with advanced renal disease have poorer prognosis and those older than 65, severe anemia, hypercalcemia, elevated blood urea nitrogen values, elevated M protein, hypoalbuminemia, and a high tumor cell burden are associated with shortened median survival times or remission

WHAT IS THE MOST IMPORTANT PROGNOSTIC INDICATOR FOR EWING SARCOMA?

• the extent of the disease at the time of the diagnosis (those with metastatic disease at dx have poorer outcome)

•  Other factors: tumor size and location

WHAT IS THE PROGNOSTIC INDICATORS OF METASTATIC BONE DISEASE? 

• depends on the primary site, histology, and degree of metastases at the time of diagnosis

 WHAT IS THE GENERAL TX OF BONE CANCERS?

• Surgery

• Neoadjuvant Chemo, Standard regimen for most primary tumors is multiagent

• EBRT is recommended on a case-by-case basis

WHAT ARE THE COMMON GENERAL CHEMO DRUGS?

• cisplatin, doxorubicin, cyclophosphamide, vincristine, methotrexate, leucovorin, etoposide (Ifosfamide is used, but not as part of the standard regimen due to its toxicity)

WHAT IS THE TX OF OSTEOSARCOMA?

• multi-D approach because it is chemosensitive and radioresistant- chemotherapy, surgical resection of the primary tumor, followed by additional chemotherapy

• Amputation is a thing of the past

• EBRT IS NOT PART OF STANDARD CARE

WHAT IS THE TX OF CHONDROSARCOMA?

• Surgical resection is the primary method of treatment

•  Wide excision of the entire mass, with adequate bone and soft tissue margins

•  EBRT not part of standard tx regimen

• Proton therapy is effective in local control 

WHAT IS THE TX OF FIBROSARCOMA?

• call for an aggressive surgical procedure with wide or radical excision

•  Not highly radiosensitive, but irradiation is recommended for inoperable tumors, postoperative residual disease, and palliation

•  High rates of recurrence are common, which warrants prophylactic radiation therapy and/or systemic therapy

•  Chemotherapy recommended for postoperative recurrence and for patients with discomfort, two primary chemo agents used: doxorubicin and ifosphamide

WHAT IS THE TX OF MALIGNANT FIBROUS HISTIOCYTOMA?

• Surgery is the initial treatment method

•  Complete local excision has been shown to prolong relapse-free survival

•  Preoperative or postoperative EBRT may be used to help improve

• local control or as a definitive treatment for inoperable lesions or in cases with positive surgical margins

WHAT IS THE TX OF GIANT CELL TUMORS?

• High recurrence rate, surgical resection which may be either a wide excision or intralesional curettage is best

•  EBRT reserved for areas where complete surgical excision is not possible and cases of advanced or recurrent disease

WHAT IS THE TX OF MULTIPLE MYELOMA?

• combination of chemotherapy and radiation therapy

•  Chemotherapy is given with a curative intent, whereas radiation is effective in controlling the pain from a bony lesion

• Autologous stem cell transplant after high-dose chemotherapy

• SURGERY IS UNCOMMON 

 WHAT IS THE TX OF EWING SARCOMA?

• Surgery, chemotherapy, and radiation therapy

•  Highly sensitive to chemotherapy, which may be given pre- or postoperatively

• Radiation therapy is typically given postoperatively, especially in cases with positive surgical margins or when resection is not possible

WHAT IS THE TX OF METASTATIC BONE DISEASE? 

• Palliative vs, curative

•  EBRT: 30-35 Gy

•  Radiopharmaceutical agents: Strontium-89 and samarium- 153

WHAT IS THE EPIDEMIOLOGY OF SOFT TISSUE SARCOMAS? 

• LOW INCIDENCE 

• MORTALITY RATE IS HIGH

• INCIDENCE HIGHER IN MEN

• Most commonly affects adults between the fifth and seventh decades of life with over 50% being diagnosed over the age of 60

WHICH SOFT TISSUE SARCOMA IS MOST COMMON IN CHILDREN UNDER SIX?

• Rhabdomyosarcoma

WHAT ARE THE TWO SUBTYPES OF SOFT TISSUE SARCOMAS?

• embryonal and alveolar

WHAT ARE THE ETIOLOGIC FACTORS OF SOFT TISSUE SARCOMAS?

• Cause unknown

•  Genetic and environmental factors

•  Prior exposure to radiation

•  Genetic conditions: most common neurofibromatosis, Li- Fraumeni syndrome, Gardner syndrome, Werner syndrome, tuberous sclerosis, and Gorlin syndrome

WHAT IS THE CLINICAL PRESENTATIONS OF SOFT TISSUE SARCOMAS?

• Nonspecific

•  Painless, gradually enlarging mass.

•  A large tumor in the abdomen or pelvis may cause pain and bloating associated with gas or constipation

WHAT IS THE PREFERRED BIOPSY METHOD FOR SOFT TISSUE SARCOMAS?

• Core needle

WHAT IS THE MOST COMMON PATHOLOGIES OF SOFT TISSUE SARCOMAS? 

• liposarcoma and leiomyosarcoma

WHAT IS USED FOR THE  GRADING AND STAGING OF SOFT TISSUE SARCOMAS? 

• The two most used primary systems for grading STS are the French Federation of Cancer Centers Sarcoma Group (FNCLCC) and the National Cancer Institute system

•  The recommended staging system is the AJCC, or TNM, system

WHAT IS THE SPREAD PATTERN OF SOFT TISSUE SARCOMAS?

• Aggressive and invade along local, anatomically defined planes composed of neurovascular structures, fascia, and muscle bundles

•  Lymphatic extension not common

WHAT IS THE PRIMARY ROUTES OF SPREAD OF SOFT TISSUE SARCOMAS?

Hematologic pathways are primary routes of spread; the lung is the most common site of metastasis, followed by the bones, liver, and skin

WHAT IS THE STANDARD OF CARE IN TX OF LOCALIZED SOFT TISSUE SARCOMAS (stage 1A, 1B)? 

• Surgical resection 

RT FOR SOFT TISSUE SARCOMAS? 

• Adjuvant: EBRT, brachytherapy, intraoperative radiation therapy (IORT), or a combination of these modalities

PRIMARY CHEMO DRUG FOR SOFT TISSUE SARCOMAS? 

• Doxorubicin