Pathology Lab-Bone I

Question 1

What does elevated alkaline phosphatase level tell you in a patient?

Answer 1

Elevated osteoblastic activity

Question 2

What do you start thinking about if you see multiple osteocytes and chondrocytes in a single lacuna?

Answer 2

Malignancy

Question 3

What is the basic, non-mineralized matrix that is first laid down in bone? What does this substance look like on an H&E stain?

Answer 3

Osteoid. It stains pink.

Question 4

What type of bone lacks structure, stains purple in H&E and is laid down after osteoid?

Answer 4

Woven bone.

Question 5

What is the final step in bone development to increase bone strength?

Answer 5

Mineralized lamellar bone formation in the direction of weight bearing

Question 6

What types of bone growth are seen in children? Adults?

Answer 6

Epiphyseal and appositional bone growth are seen in children. Appositional bone growth is the only form of bone growth in adults.

Question 7

A 74 year old woman tripped and was unable to get up. She has noticed instability in dance exercises recently. You sent her to get a dexascan which confirmed osteoporosis. How is her condition different from someone with osteomalacia?

Answer 7

People with osteomalacia have a reduction in mineralization. Osteoporosis is simply a decrease in bone mass, all blood tests will be the same as someone without osteoporosis.

Question 8

Why do menopausal women have an increased risk for osteoporosis?

Answer 8

Women produce more pro-inflammatory cytokines in the absence of estrogen. One of these is TNF, which increases expression of RANK and RANKL which increases osteoclast activity.

Question 9

Why do young people sometimes get osteoporosis (secondary osteoporosis)?

Answer 9

Disuse, drugs, endocrine, neoplasia.

Question 10

What are some factors that indicate osteoporosis that can tip you off without the patient breaking a bone?

Answer 10

Change in posture, change in height (due to loss of vertebral height) and, the gold standard, DXA Scan

Question 11

What can you prescribe to an older person with osteoporosis?

Answer 11

Vitamin D, exercise, estrogen supplementation, and anti-inflammatory drugs.

Question 12

What is your diagnosis?

Answer 12

Osteoporosis. Note lack of trabecullar interconnections, thin trabeculae, quiescent cellular activity, and thin cortex.

Question 13

A 65 year old woman complains of pain in her back, knees and hips for several years. During your physical exam you note Heberden nodes and no swelling or redness in the joints. What is causing her symptoms?

Answer 13

This is typical of degenerative join disease. Cartilage degeneration causes friction and pain in the joints.

Question 14

A 65 year old woman complains of pain in her back, knees and hips for several years. During your physical exam you note Heberden nodes, swelling and redness in the joints. What is your differential diagnosis? What tests could you do?

Answer 14

Gout, pseudogout, septic infection or rheumatoid arthritis. Culture, gram-stain, biopsy looking for inflammatory cells and crystals.

Question 15

How does your body compensate for cartilage degeneration by stabilizing joints?

Answer 15

Formation of osteophytes. Also note area of yellow fibrosis due to bone on bone friction.

Question 16

A patient comes to see you with knee pain and is wondering if he will need a knee replacement in the future. This is his biopsy, what do you tell him?

Answer 16

He has degenerative joint disease, his cartilage is fraying away and will need a knee replacement.

Question 17

A 57 year old female with right leg pain for the last 3 months comes to see you. During your physical exam you notice anterior bowing of the tibia, warmth and localized tenderness over the skin of the bone. You order an x-ray and it shows expansion and alternating areas of osteosclerosis and osteolysis. Why is this person at risk for fractures?

Answer 17

This is Paget’s Disease. Rampant osteoblast overcompensation for initial osteoclast overactivity creates a disorganized, weak and mosaic pattern of woven bone. Although the woven bone is later converted to lamellar bone, it is still weak and prone to fracture.

Question 18

How do you know this patient does not have bone loss due to osteoporosis?

Answer 18

Giant osteoclasts are taking bites out of the bone and osteoblasts are working to build bone. The highly cellular surface indicates tremendous bone turnover typical of Paget’s disease.

Question 19

How does hyperparathyroidism differ from Paget’s disease?

Answer 19

Lots of osteoclast activity and little osteoblast activity. You will also have high blood Ca levels and PTH levels not evident in Paget’s disease.

Question 20

What do blood samples look like in a patient with Paget’s disease?

Answer 20

Alkaline phosphatase will be very high and Ca levels will be normal because it is being recycled.

Question 21

Your patient has severe polyostotic Paget’s disease. What is your greatest concern for this patient?

Answer 21

Polyostotic Paget’s disease creates a fertile ground for osteosarcomas.

Question 22

What bones are typically affected in Paget’s disease?

Answer 22

Skull, tibia and pelvis.

Question 23

A 15 year old boy presents with pain, swelling and lack of mobility in the knee. What do you see in this x-ray and what condition does it hint towards?

Answer 23

Note Codman’s Triangle evident by destruction of the cortex which shows malignancy. This hints toward osteosarcoma.

Question 24

Why is a tissue sample not enough to make a diagnosis of osteosarcoma?

Answer 24

Osteoblasts intimately associated with the osteoid they are making is typical of osteosarcoma AND bone fractures.

Question 25

When is osteosarcoma considered a secondary condition?

Answer 25

In people with Paget's disease

Question 26

What familial mutation has a 100 fold increased risk of osteosarcoma?

Answer 26

Hereditary Retinoblastoma with a mutated RB tumor suppressor gene.

Question 27

Why do people with LiFraumeni Syndrome have an increased risk for osteosarcoma?

Answer 27

They have a loss of p53 tumor suppressor gene.

Question 28

What is them most common tumor suppressor gene mutation in osteosarcoma?

Answer 28

p53

Question 29

A 45 year old man presents with hip pain lasting for the past 4 months. Imaging reveals a destructive lesion involving the body of the left ischium. The lesion is excised and looks like this. What was it? What would your expect to see in a radiograph?

Answer 29

This is a chondrosarcoma, not lobules of gray-white tissue with "soap bubble" appearance. In a radiograph you would expect to see dystrophic calcification.

Question 30

What do you look for in this slide if you are thinking about a diagnosis of chondrosarcoma?

Answer 30

Cellular crowding, disorganization and more than one nucleus in a lacuna.

Question 31

How do chondrosarcomas and osteosarcomas differ in location and metastasis?

Answer 31

Osteosarcomas are usually around the knee and metastasize to the lung early on. Chondrosarcomas are usually in the axial skeleton, grow slowly and have a low metastasis rate.

Question 32

A 35 year old woman presents with recurrent pain, swelling, loss of movement and deformities in the joint of the hand. She also has morning stiffness lasting 20-30 minutes. What is causing her symptoms?

Answer 32

This is an autoimmune reaction against synovium that causes rheumatoid arthritis. Inflammatory mediators spill over into cartilage and bone, resulting in loss of joint integrity.

Question 33

What is this called if you know you are looking at a joint?

Answer 33

Pannus. Note inflammatory cells attacking the joint tissue and forming a granuloma, this is common in rheumatoid arthritis.

Question 34

How would this look grossly?

Answer 34

This is a rheumatoid nodule due to histiocyte formation of loose granulomas around areas of necrosis

Question 35

A 40 year old female comes to see you with a tender bump in her retroperitoneum. She was treated 20 years earlier with radiation for another malignant tumor. What is the most likely diagnosis of this soft-tissue tumor?

Answer 35

Malignant fibrous histeocytoma. This is the most common type of soft-tissue sarcoma that arises from irradiation

Question 36

A 20 year old comes to see you after being hit in the arm with a baseball. It is red and swollen, no breaks so you send him home with NSAIDs. He comes back three weeks later and the bump has turned into a hard, confined nodule in his arm. What is the most likely diagnosis?

Answer 36

Nodular fasciitis. These often occur in the soft tissue after a traumatic injury

Question 37

What signals increase and what signals decrease as a result of post-menapausal estrogen decrease?

Answer 37

IL-1, IL-6 and TNF all increase. This causes a decrease in OPG and increases in RANK and RANKL. This causes an overall increase in osteoclast activity.

Question 38

What is the most common sarcoma of adults?

Answer 38

Liposarcoma

Question 39

A patient comes to see you with a bump underneath his knee cap near the quadriceps. How does this type of tumor arise in the joint and outside of the joint?

Answer 39

Synovial sarcomas arise not only from synovium, but also from mesenchyme in the soft-tissue.

Question 40

What predisposes someone from getting arthritic joint pain after a shigella infection?

Answer 40

HLA-B27 allele

Question 41

How do brown tumors come about in primary hyperparathyroidism?

Answer 41

PTH increases osteoclast activity =\> bone microfractures and hemorrhage =\> osteoclast AND fibroblast infiltration

Question 42

A patient comes to see you complaining of pain in her hand and cannot straighten one of her fingers (Dupuytren contracture). You notice a cord-like bump on the dorsal side of her hand. What is the bump likely made of?

Answer 42

Collagen. Dupuytren contractures are typical of superficial fibromatoses.