Systems Pathology I - Exam 2 (Part 1 -- Primary Bone Tumors)

T/F: Primary bone tumors are more common than metastasis to bone.

FALSE

-- Metastasis TO bone is MC

What are 5 features of Primary Bone Tumors?

1) Asymptomatic

2) Gradually-increasing bone pain (slow growing)

3) Mass

4) Pathogenic fracture

5) Fever, fatigue, cachexia

T/F: Benign tumors are more common than bone cancers (malignancies).

TRUE

But primary bone tumors can be either benign or malignant

What are the three most common primary bone cancers?

1) Osteosarcoma

2) Chondrosarcoma

3) Ewing Sarcoma

On an Xray, what is the darker, less dense bone? What are the brighter, more dense bone?

Darker = Radiolucent

Brighter = Radiopaque

What are two risks of bone tumors?

1) Mutations of RB or TP53

2) Inflammation (ex: AVN, hardware, ect)

What are the three different categories of bone tumors?

1) Bone-forming tumors

2) Cartilage forming tumors

3) Tumor or unknown origin

What category of tumors produce bony tissue that has variable levels of mineralization, likely to manifest with poorly-mineralized osteoid and mineralized woven bone? Are these benign or malignant? How is it diagnosed?

Bone-forming tumors

-- benign OR malignant

-- Biopsy confirms diagnosis

What are the two main types of Bone-forming tumors?

1) Osteoid osteoma / Osteoblastoma

2) Osteosarcoma

Is an Osteoid Osteoma benign or malignant?

Benign

What is the size of an Osteoid Osteoma?

<2 cm

What is the location that an Osteoid Osteoma is most commonly found?

Cortex (metaphysis) of tibia/fibula

What is the most common age and gender of Osteoid Osteoma?

10-20

MALES (2x)

Does Osteoid Osteoma affect bone, cartilage, or is it unknown?

Bone

What is a characteristic radiogarphic appearance of an Osteoid Osteoma?

Round to oval lesion near the cortex with a central "nidus" with a rim of sclerosis

NOTE: also commonly see an open growth plate...

What type of pain is experienced in Osteoid Osteoma? Can it be relieved?

Localized nocturnal pain

-- relieved by aspirin/NSAIDs

Is an Osteoblastoma benign or malignant?

Benign

What is the size of an Osteoblastoma?

2+ cm (2-6 cm)

Where is an Osteoblastoma most commonly found in the body?

Spine (vertebral processes/vertebral column)

What age and gender is most commonly affected by Osteoblastoma?

10-20

MALES

Does Osteoblastoma affect bone, cartilage, or unknown?

Bone

What type of pain is experienced in Osteoblastoma? Can this pain be relieved?

Poorly localized nocturnal pain

-- unrelieved by aspirin

What is the treatment for Osteoblastoma?

Excision or possible irradiation

Is an Osteosarcoma benign or malignant?

Malignant

(& very aggressive!)

NOTE: remember this is the msot common primary bone cancer, making up 20% of all primary bone cancers

What is the size of an Osteosarcoma?

Fairly large

What is the location that an Osteosarcoma is most commonly found?

Metaphysis of bones that make up knee most commonly (distal femur, proximal tibia & humerus)

- can also be bones making up hip or shoulder

What age and gender does an Osteosarcoma most commonly affect?

10-20

Males (x1.5)

Does Osteosarcoma affect bone, cartilage, or unknown?

Bone

If an Osteosarcoma is seen in an age >40 years old (which it is most commonly seen in 10-20 years old), its typically associated with bone irritation through what? What is the prognosis?

Paget disease, AVN, irradiation

- Worse prognosis (poor response to therapy and typically lethal)

NOTE: This is a secondary Osteosarcoma

What is the common locations of a secondary Osteosarcoma?

Femur, humerus, and pelvis

What is a distinct radiographic feature of an Osteosarcoma?

Periosteal reactions such as the Codman triangle (MC) or "sunburst"

Is an Osteosarcoma Lytic or blastic?

BOTH

Osteosarcoma consists of irregular bone due to mixed mineralization (bone building and bone lysis together)

--> Osteoid formation

What is Codman triangle?

Destroyed periosteum and medullary cavity, raising the periosteum as it grows

What is the pain level for an Osteosarcoma? What gene mutations is it linked to?

Painful, rapidly-enlarging mass

-- RB & TP53 mutations are common

(Retinoblastoma syndrome = 1000x risk)

Up to 20% of Osteosarcomas have metastasized to _____ by the time of diagnosis?

Lungs

What is the survival rate of a typical Osteosarcoma?

60-70% long-term survival rate due to:

- ability to amputate

- chemotherapy

What general category of bone tumors will produce bony hyaline (glass-like/clear) or myxoid (mucus-like) cartilage?

Cartilage-Forming Bone tumors

Are benign or malignant tumors more common for cartilage-forming bone tumors?

Benign

What are the three main types of Cartilage-Forming Bone tumors?

1) Osteochondroma (exostosis)

2) Chondroma (enchondroma)

3) Chondrosarcoma

Is an Osteochondroma (exostosis) benign or malignant?

Benign

What is the size of an Osteochondroma (exostosis)?

fairly large (1-20cm)

What is the most common location where Osteochondroma (exostosis) are found?

Metaphysis of long bones near growth plate

- MC that make up knee

(can also do pelvis, scapula, ribs, hands/feet)

What is the most common age and gender affected by Osteochondroma (exostosis)?

10-30 year old

Males

Which type of cartilage does an Osteochondroma (exostosis) affect?

Hyaline cartilage

-- cartilage-capped outgrowth

Is Osteochondroma (exostosis) hereditary of sporadic? Is it YA onset or childhood onset?

Can be either; commonly its an incidental diagnosis

--> Solitary = Sporadic in adolescent/young adult onset

--> Hereditary = Multiple hereditary osteochondromas (familiar, mutated TSGs, childhood onset)

Does an Osteochondroma (exostosis) have a fast onset or slow? What kind of pain does it demoonstrate?

Develops slowly

-- usually asymptomatic

Will be painful if fractured or begins to compress other tissues

What is an Osteochondroma that manifests with a narrow base of attachment to the host bone? What is an Osteochondroma that manifests with a broad base of attachment?

Narrow = Pedunculated

Broad = Sessile

What is the risk of an osteochondroma (exostosis) becoming cancerous? What cancer would this be?

<1%

-- chondrosarcoma

Which type of Osteochondroma (exostosis), hereditary (multiple hereditary osteochondromas) or solitary, has a higher risk for malignant transformation?

Hereditary (Multiple hereditary osteochondromas)

Is an Enchondroma (Chondroma) benign or malignant?

Benign

(10% of all benign bone tumors)

What is the size of an Enchondroma?

Fairly small

Where is an Enchondroma most commonly found?

Bones of the hands

-- less commonly in feet

What is the most common age and gender that Enchondroma (Chondroma) affects?

20-50

Males

What type of cartilage does Enchondroma affect?

Hyaline cartilage

-- gray-blue nodules

Naming of a Chondroma is based on its location. Which type is in the medullary cavity? Which type is cortical?

Medullary = Enchondroma

Cortical = Juxtacortical chondroma

What pathology is multiple enchondromas, resulting of sporadic mutations?

Ollier disease

What are 2 distinctive radiographic features of Enchondroma?

Well-circumscribed lucency

1 -- ring of sclerosis = "o-ring"

2 -- possible osteonecrosis (AVN) in center with irregular calcifications

Is Enchondroma symptomatic or asymptomatic?

MC asymptomatic with incidental diagnosis

--> possible pathologic fractures

What is the 2nd most common primary bone tumor?

Chondrosarcoma

Is Chondrosarcoma malignant or benign?

Malignant

What is the size of a Chondrosarcoma?

Fairly large

Where are Chondrosarcoma most commonly found? Is it most commonly intramedullary or juxtacortical?

Bone of shoulder & pelvic girdle

-- rare in distal extremities

Can be both but most commonly intramedullary

What age and gender is most commonly affected by Chondrosarcoma?

40-60

Males

What kind of mass (distinctive feature) can be observed in Chondrosarcoma?

"Glistening" mass

-- neoplastic cartilage

Does a Chondrosarcoma thicken or erode the bone cortex?

Can do either

(especially when expanding within medullary cavity)

What is a distinctive radiographic appearance of Chondrosarcoma? What does an increased radiolucency indicate?

"Stippled" or "popcorn" calcifications

-- Increased radiolucency = increased high-grade chondrosarcoma

(radiolucency sign of aggressiveness)

Which type of Chondrosarcoma is the most common, slow growing (indolent) and small, causing thickening of the cortex and having a favorable prognosis (90% 5 year survival)?

Low-grade Chondrosarcoma

Which type of Chondrosarcoma is a large mass that erodes cortex, with 70% metastasizing to lungs (MC) or other bones, with a poorer prognosis and about a 40% survival?

High-grade Chondrosarcoma

What is the pain level in Chondrosarcoma? What is its treatment?

Painful mass

Treatment = wide excision & chemotherapy

What is the difference between the morphologies of an Osteochondroma, Chondroma (Enchondroma), and a Chondrosarcoma?

Osteochondroma = bony outgrowth, cartilaginous cap

Chondroma (Enchondroma) = Well-circumscribed, solitary (MC), resemble normal cartilage

Chondrosarcoma = thickening or erosion of cortex, soft tissue mass, radiolucency --> aggressiveness

What are two types of Fibrous & fibro-osseous bone tumors?

1) Fibrous cortical defect (Nonossifying fibroma)

2) Fibrous Dysplasia

What are two types of bone tumors with unique cells?

1) Ewing Sarcoma (Primitive Neuroectodermal tumor (PNET))

2) Giant-Cell tumor or bone

Is Fibrous Cortical defect (FCD) & Nonossifying Fibroma (NOF) benign or malignant?

NOT considered a neoplasm; may be reaction to periosteal injury

-- but could be benign proliferation of fibroblasts & macrophages

What is the size of Fibrous Cortical Defect? Nonossifying Fibroma (NOF)?

<3cm

If larger than 3cm, known as Non-ossifying fibroma

NOTE: 1/2 occur as multiple (not just one)

Where is Fibrous Cortical defect (FCD) & Nonossifying Fibroma (NOF) most commonly found?

Metaphysis or Diaphysis (near cortex) of lower extremity long bones

-- MC knee

What age group is Fibrous Cortical defect (FCD) & Nonossifying Fibroma (NOF) most common in?

Children

--> VERY common affecting 40% of all children

Does Fibrous Cortical defect (FCD) & Nonossifying Fibroma (NOF) affect bone, cartilage, or other?

Fibrous tissue

Is Fibrous Cortical defect (FCD) & Nonossifying Fibroma (NOF) symptomatic or asymptomatic? How is it resolved?

Asymptomatic; if large may fracture though

-- Self-resolve over few years and develops into cortical bone

-- biopsy not required except if fractured NOF

What is failed bony differentiation with arrested development (failed osteoblast differentiation), and is a widely variable condition that may be asymptomatic, painful, a deformity, or fracture?

Fibrous Dysplasia (FD)

Is Fibrous Dysplasia (FD) benign or malignant?

Benign proliferation of fibrous tissue & woven bone

What is the size of Fibrous Dysplasia (FD)?

Fairly large

-- variable in size and # of sites

Where is Fibrous Dysplasia (FD) found in the body?

WIDESPREAD

(ribs, calvaria, mandible, femur, humerus)

What age group is most commonly affected by Fibrous Dysplasia (FD)?

Childing (lasting into adulthood)

Does Fibrous Dysplasia (FD) affect bone, cartilage, or other?

Fibrous tissue

What causes Fibrous Dysplasia (FD)?

Spontaneous GNAS mutations

What are the three types of Fibrous Dysplasia (FD) based on the GNAS mutation?

1) Monostotic --> single bone involved

2) Polyostotic --> multiple bones involved

3) McCune-Albright syndrome

Which type of Fibrous Dysplasia (FD) is MC, affecting ages 10-30, widespread (ribs, femur, tibia, jawbones, calvaria, humerus) with little or no bony distortion, and is asymptomatic?

Monostotic FD

Which type of Fibrous Dysplasia (FD) is seen in late childhood/adolescents, widespread (femur, calvaria, tibia, humerus, pelivs) with severe deformation, commonly resulting in fractures and craniofacial involvement (50% of cases)?

Polyostotic

What is a radiographic feature of Polyostotic Fibrous Dysplasia?

Well-defined "ground-glass" appearance

What is the treatment for Polyostotic Fibrous Dysplasia?

Excision

-- possible ortho hardware

Which type of Fibrous Dysplasia (FD) is 3% of cases involving bony lesions (skeletal), cafe au lait spots (skin), and endocrine hyperfunctioning (endocrinopathy)?

McCune-Albright Syndrome

Where is the most common location for bony lesions in McCune-Albright Syndrome?

Unilateral in femur or tibia

What is the Cafe au lait spotsin McCune-Albright Syndrome associated with? Who is it most commonly diagnosed in?

Precocious puberty prompts evaluation

-- MC diagnosis in FEMALES

What can the endocrine hyperfunctioning result from? (3) What can it cause in McCune-Albright Syndrome?

Results from:

1) Hyperthyroidism

2) Pituitary adenoma

3) Adrenal hyperplasia

Can cause

- early puberty

What are two variants of the same malignancy (t(11;22) or t(21;22)) causing small round-cell tumors of bone?

Ewing Sarcoma & Primitive Neuroectodermal Tumor (PNET)

Is Ewing Sarcoma benign or malignant?

Malignant

What is the size of Ewing Sarcoma?

"fairly large"

Where is Ewing Sarcoma most commonly found?

Diaphysis of long bones

-- MC femur

What age and gender is more commonly affected by Ewing Sarcoma?

10-20 year old

Males

Caucasian

Does Ewing Sarcoma affect bone, cartilage, or other?

Primitive small round cells