Pathology- Ch. 26 Bone Part Flashcards by Ben Dover

What is mutated in Achondroplasia?

-Caused by a mutation in FGFR3

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What does the mutation in FGFR3 cause?

-inhibits cartilage proliferation and supresses growth

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What is the difference between heterozygotes and homozygotes with achondroplasia?

Heterozygotes have a normal life span
Homozygotes do not live long

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What are the signs of achondroplasia?

Shortened extremities, normal sized trunk, enlarged head, bulging forehead, and depression of the root of the nose.

-Most common cause of dwarfism

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Which of the osteogenisis imperfectas (OI) is the only mainly autosomal recessive one?

Type II (Lethal)

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Which OI types are autosomal dominant?

Type I

Type III (75% dom, 25% recessive)

Type IV

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What is the cuase of OI type I?

decreased synthesis of alpha-1, and abnormal pro-alpha1 or pro-alpha2 chains
postnatal fractures, blue sclara, normal stature, hearing impairment

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Does OI type I get better or worse with age?

-better

–>generally improves with puberty

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What is the cause and sign of OI type II?

-abnormal pro-alpha 1 and 2 result in unstable triple helix

–> **Lethal in utero or shortly after birth **

-Sever fratures and deformity (blue sclara)

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What is the major cause and signs of OI type III?

-altered pro-alph2 lead to impaired formation of the tripple helix

–> growth retardation, fractures, **progressive kyphoscoliosis, blue sclara becoming white **

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Does OI Type III improve or worsen with age?

-It is progressive and gets worse with age

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What is the major cause of OI type IV?

Short pro-alpha2 (unstable tripple helix)

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What are the major differeneces between OI Type I and IV?

Type IV–> normal sclara and short stature

Type I–> blue sclara and normal stature

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What is the main cause of osteopetrosis?

-reduced bone resorbtion due to impaired osteoclast activity–> brittle bones

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What is the most common mutation associated with osteopetrosis?

-mutation in carbonic anhydrase II (CA II) which normally generates protons from CO2

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What is the effect of impaired CA II function?

-no acidification of the resorbtion pit and the urine

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What are other causes of osteopetrosis?

-defective Cl channel, proton pump and RANKL

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What is Paget disease of bone?

-increase in osteoclast activity

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What is the transmission pattern of Paget Disease of Bone?

Autosomal Dominant

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What are the three stages of osteopetrosis?

(1) Osteolytic Stage
(2) Mixed osteoclastic-osteoblastic stage
(3) burnt out quiescent osteosclerotic stage

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What is the reason for bone weakness in Paget disease?

The bone is massive, but is haphazardly laid down and structurally unstable and unsound

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How does on differentiate Paget disease of bone and osteopetrosis?

Paget is a late onset
Osteopetrosis is an earlier onset disease

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What is a diagnostic feature of patients with Paget disease of bone?

Increase serum alk. phos.
Increased urine hydroxyproline

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What tumor are associated with Paget disease?

-osteosarcoma

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What causes rickets in children?

-Vitamin D deficiency

What is rickets called in adults? What is the cause?

- Osteomalacia - defective mineralization of bone that has completed development

What is the difference between primary and secondary hyperparathyroidism?

- Primary: autonomous hyperplasia or parathyroid adenoma - secondary: prolonged hypocalcemia--\> compensatory hypersecretion of PTH

What is the overall effect of PTH?

Increase Ca resorption and reuptake and increase serum Ca levels

What are the four skeletal changes associated with chronic renal disease?

- increased osteoclast activity - delayed matrix remineralization (osteomalacia) - osteosclerosis - growth retardation

Retention of what chemical causes the cascade that leads to renal osteodystrophy?

Phosphate retention

What is osteomyelitits?

inflammation of the bone marrow caused by infection.

What is the most common cause of pyogenic osteomyelitits?

Staph. aureus

What is the most common area of infection for tuberculous osteomyelitis?

Thoracic and lumbar spine

What bones are most often affected in skeletal syphylis?

-nose, palate, skull and long bones of the extremities

- A patient complains of severe nocturnal pain that is alleviated by aspirin. A 1.5cm mass is discovered somewhere in the apendicular skeleton. - What most likely describes the mass?

Osteoid Osteoma

Another patient complains of pain in the lower spinal area. The pain is dull, achy and no relief is achieved with aspirin or other salicylates. A mass of 3cm greatest dimension is discovered. -What most likely describes the mass?

-Osteoblastoma

What is a characteristic action of osteosarcomas?

-produce bony matrix

Are ostoesarcomas malignant?

Yes

A 25 year old male presents with swelling in his left knee and intense pain. A large gray-white gritty growth is discovered with Codman triangles, and biopsied. P53 and RB mutations are both present as well as tumor giant cells with hyperchomatic nuclei. What is the diagnosis?

Osteosarcoma

What are the two age groups that are most affected by osteosarcomas?

-2nd decade and then late in life (can be attributed to paget disease)

What is the most coomon benign bone tumor?

Osteochondroma

What is mutated in an osteochondroma caused by multiple hereditary exostosis syndrome?

EXT1 and EXT2

What is the usual shape of the osteochondroma?

Mushroom shaped

What is a chondroma?

-benign tumor or hyaline cartilage that occur in bones of encondral origin

Where does an enchondroma occur? How about a subperiosteal or juxtacortical chondroma?

- Enchondromas occur in the medullary cavity - Subp. and juxt. chondromas occur on the surface of the bone

What is ollier disease? How does it differ from maffucci syndrome?

- disease of multiple enchonromas - Maffucci syndrom is associated with hemangiomas as well

A **17 year old male** presents with a painful growth in the **knee**. The growth is biopsied and a **chicken wire pattern** of mineralization is noted with **necrosis** and mitotic acitivty. - It is noted that the tissue is composed of sheets of compact polyhedral chonroblasts that have defined borders, pink cytoplasm and hyperlobulated nuclei. - What is the diagnosis? Is it rare?

- Chondroblastoma - Rare

What is the prevalence of chondromyxoid fibromas?

- rarest of the cartilage tumors - more coomon in med in their 20's

What is the morphology of a chonromyxoid fibroma?

- 3 to 8cm - glistening tan-gray - large hyperchromatic nuclei and non-neoplastic osteoclast tybe giant cells - cell processes that extend through the matrix and touch eachother

What are the most common sites of the malignant chondrosarcoma?

- **Shoulder** - pelvis - proximal femur and ribs

What is the preferential tissue of spread for the chondrosarcoma?

-lungs and skeleton

Are chondrosarcomas more common later in life or early in life?

Later in life, 40s and older

What is the most common age rang of fibrous corical defects? w big are they usually and what if they get bigger?

- most common in children (\>2y/o) - Normally no more than 0.5cm, but if they grow upwards of **5 or 6cm** they are then classified as **non-ossifying fibromas. **

What is the morphilogical appearance of non-ossifying fibromas?

- sharply demarcated radilucencies that are surrounded by a thin fim of sclerosis - also contain multinucleated giant cells or clusters of foamy macrophages

What causes fibrous dysplasia?

- Gain-of-function mutation in the GNAS gene. - production of hyperactive guanyl nucleotie binding protein which lead to abnormal growth

What are the symptoms of McCune-Albright Syndrome?

-polyostotic fibrous dysplasia associated wtih cafe-au-lait skin pigmentation

What is a characteristic histalogical appearence of fibrous dysplasia?

-shapes of trabeculae tha mimic Chinese letters

What are fibrosarcomas?

-Collagen producing sarcomas with a fibroblastic phenotype

What is the mophology of a fibrosarcoma?

-large, **hemorrhagic**, tan-white masses that destroy the underlying bone and extend into soft tissue

What is the difference between PNET (primitive neuralectodermal tumor) and EWS (Ewing Sarcoma)?

- EWS are not differentiated - PNETs are neurally differentiated

What is the mutation involved in EWS family of tumors?

translocation: (11;22) (q24;q12)

What is the appearence of EWS and PNET?

- arise in the medullary cavity, indave the cortex, periosteum and soft tissue. - soft tan-white and contain areas of hemorrhage and necrosis

What color is a giant-cell tumor?

Red-brown

Are giant-cell tumors malignant or benign? Where do they normally arise?

- benign but locally agressive - around the knee - 20-40's

What are the most common origins of skeletal metastases in adults?

-prostate, breast, kidney, lung

Most common origins of skeletal metastases in children?

- neuroblastoma - Wilms tumor - osteosarcoma - EWS - Rhabdomyosarcoma