Musculoskeletal, Skin, and Connective Tissue- Phatology

Question 1

Achondroplasia

Answer 1

Failure of longitudinal bone growth (endochondral ossification) Ž short limbs.

Constitutive activation of FGFR3 actually inhibits chondrocyte proliferation. > 85% of mutations occur
sporadicall.

Associated with increased paternal age. Most common cause of dwarfism.

Question 2

Osteoporosis

• Definition
• Diagnosis

Answer 2

bone lose mass despite normal bone mineralization and lab values.

Diagnosed by bone mineral density measurement by DEXA at the lumbar spine, total hip, and femoral neck, with a T-score of ≤ −2.5 or by a fragility fracture at hip or vertebra.

Question 3

Osteoporosis

• Occurs in
• Treatment

Answer 3

Most commonly due to bone resorption related to low estrogen levels and old age.

Treatment: bisphosphonates, teriparatide, SERMs, rarely calcitonin; denosumab (monoclonal antibody against RANKL).

Question 4

vertebral compression fractures (in osteoporosis)

Answer 4

acute back pain, loss of height, kyphosis. Also can present with fractures of femoral neck, distal radius (Colles fracture).

Question 5

Osteopetrosis

• Definition
• Etiology
• Imagen

Answer 5

Defective osteoclasts Ž thickened, dense bones that arecprone to fracture.

Mutations (eg, carbonic anhydrase II) impair ability of osteoclast to generate acidic environment. Fills marrow space Ž pancytopenia, extramedulla ry hematopoiesis

X-rays show diffuse symmetric sclerosis (bone-in-bone, “stone bone”). Bone marrow transplant is curative.

Question 6

Osteomalacia/rickets

- Etiology

Answer 6

Defective mineralization of osteoid (osteomalacia) or cartilaginous growth plates (rickets). Most commonly due to vitamin D deficiency. Increase ALP

Question 7

Osteomalacia/rickets

• Imagen
• Clinical presentation

Answer 7

X-rays show osteopenia and “Looser zones” (pseudofractures) in osteomalacia, epiphyseal widening and metaphyseal cupping/fraying in rickets.

Children with rickets have pathologic bow legs (genu varum), bead-like costochondral junctions (rachitic rosary), craniotabes (soft skull).

Question 8

Paget disease of bone (osteitis deformans)

- Physiophatology

Answer 8

Increase osteoclastic activity followed by increase osteoblastic activity that forms poor-quality bone. Mosaic pattern of woven and lamellar bone; long bone chalk-stick fractures.

High blood flow from High arteriovenous shunts may cause high-output heart failure. High risk of osteogenic sarcoma.

Question 9

Paget disease of bone (osteitis deformans)

• Clinical presentation
• Stages
• Treatment

Answer 9

Hat size can be increased due to skull thickening; hearing loss is common due to auditory foramen narrowing.

Stages of Paget disease:
ƒƒ Lytic—osteoclasts
ƒƒMixed—osteoclasts + osteoblasts
ƒƒ Sclerotic—osteoblasts
ƒƒQuiescent—minimal osteoclast/osteoblast activity

Treatment: bisphosphonates.

Question 10

Osteonecrosis (avascular necrosis)

Answer 10

Infarction of bone and marrow, usually very painful. Most common site is femoral head.

“CAST Bent LEGS.”
Corticosteroids, Alcoholism, Sickle cell disease, Trauma, “the Bends” (caisson/ decompression disease), LEgg-Calvé-Perthes disease, Gaucher disease, Slipped capital femoral epiphysis.

Question 11

Lab values in bone disorders

Answer 11

Pag. 451

Question 12

Osteochondroma

• Epidemiology
• Location
• Characteristics

Answer 12

Most common benign bone tumor. Males < 25 years old.

Metaphysis of long bones

Lateral bony projection of growth plate covered by cartilaginous cap.

Question 13

Osteoma

• Epidemiology
• Location
• Characteristics

Answer 13

Middle age.

Surface of facial bones.

Associated with Gardner syndrome.

Question 14

Osteoid osteoma

• Epidemiology
• Location
• Characteristics

Answer 14

Adults < 25 years old. Males > females.

Cortex of long bones.

Presents as bone pain (worse at night) that is relieved by NSAIDs. Bony mass (< 2 cm) with radiolucent osteoid core

Question 15

Osteoblastoma

• Location
• Characteristics

Answer 15

Vertebrae.

Similar histology to osteoid osteoma. Larger size (> 2 cm), pain unresponsive to NSAIDs.

Question 16

Chondroma

• Location
• Characteristics

Answer 16

Medulla of small bones of hand and feet.

Benign tumor of cartilage

Question 17

Giant cell tumor

• Epidemiology
• Location
• Characteristics

Answer 17

20–40 years old.

Epiphysis of long bones (often in knee region).

Locally aggressive benign tumor. Neoplastic mononuclear cells that express RANKL and reactive
multinucleated giant (osteoclast-like) cells. “Osteoclastoma.” “Soap bubble” appearance on x-ray

Question 18

Osteosarcoma

• Epidemiology
• Predisposing factors

Answer 18

Accounts for 20% of 1° bone cancers. Peak incidence of 1° tumor in males < 20 years.

Predisposing factors: Paget disease, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome.

Question 19

Osteosarcoma

• Location
• Characteristics

Answer 19

Metaphysis of long bones (often in knee region)

Malignant osteoblasts. Presents as painful enlarging mass or pathologic fractures. Codman triangle (from elevation of periosteum) or sunburst pattern on x-ray.

Question 20

Chondrosarcoma

• Location
• Characteristics

Answer 20

Medulla of pelvis and central skeleton.

Tumor of malignant chondrocytes.

Question 21

Ewing sarcoma

• Epidemiology
• Location

Answer 21

Most common in Caucasians. Generally boys < 15 years old.

Diaphysis of long bones (especially femur), pelvic flat bones.

Question 22

Ewing sarcoma

- Characteristics

Answer 22

Anaplastic small blue cells of neuroectodermal origin (resemble lymphocytes). “Onion skin” periosteal reaction in bone.

Differentiate from conditions with similar morphology (eg, lymphoma, chronic osteomyelitis) by testing for
t(11;22) (fusion protein EWS-FLI1).

Aggressive with early metastases, but responsive to chemotherapy.

• 11 + 22 = 33 (Patrick Ewing’s jersey number).

Question 23

Osteoarthritis and rheumatoid arthritis

Answer 23

Pag 454

Question 24

Gout

• Definition
• Physiophatology
• Crystals

Answer 24

Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals in joints.

Hyperuricemia, which can be caused by:
ƒƒ Underexcretion of uric acid (90% of patients)—largely idiopathic.
ƒƒOverproduction of uric acid (10% of patients)—Lesch-Nyhan syndrome, PRPP excess, cell turnover (eg, tumor lysis syndrome), von Gierke disease

Crystals are needle shaped and ⊝ birefringent under polarized light.

Question 25

Gout

- Clinical findings

Answer 25

Asymmetric joint distribution. Joint is swollen, red, and painful. Classic manifestation is painful MTP joint of big toe (podagra)

Acute attack tends to occur after a large meal with foods rich in purines, trauma, surgery, dehydration, diuresis, or alcohol consumption.

Question 26

Gout

- Treatment

Answer 26

Acute: NSAIDs (eg, indomethacin), glucocorticoids, colchicine.

Chronic (preventive): xanthine oxidase inhibitors (eg, allopurinol, febuxostat)

Question 27

Calcium pyrophosphate deposition disease (pseudogout)

• Etiology
• Clinical presentation

Answer 27

Deposition within the joint space. Occurs in patients > 50 years old. Usually idiopathic, sometimes associated with hemochromatosis, hyperparathyroidism, joint trauma.

Pain and swelling with acute inflammation (pseudogout) and/or chronic degeneration (pseudo-osteoarthritis). Knee most commonly affected joint

Question 28

Calcium pyrophosphate deposition disease (pseudogout)

• Findings
• Treatment

Answer 28

Chondrocalcinosis (cartilage calcification) on x-ray. Crystals are rhomboid and weakly ⊕ birefringent under polarized light.

Acute treatment: NSAIDs, colchicine, glucocorticoids.
Prophylaxis: colchicine.