Ch14 Bone Path (Part II)

Question 1

What is the other name for PAGET Disease of bone?

Answer 1

OSTEITIS DEFORMANS

Question 2

Name that bone pathology: is characterized by abnormal, anarchic resorption and deposition of bone, resulting in skeletal distortion and weakening

Answer 2

Paget Disease of Bone

Question 3

What is the 2nd most common metabolic bone disorder behind osteoporosis?

Answer 3

Paget Disease of bone

Question 4

LETS GET IT: GENETIC mutation for Paget Disease of bone…also, what % of familial cases and what % of sporatic cases have this mutation? what is the mutation effect on severity?

Answer 4

germline mutation in the seqestosome 1 gene (SQSTM1) AKA p62..found in 40% of familial cases and 8% of sporatic cases, more severe disease WITH the mutation

Question 5

Mechanism of Paget: SQSTM1 activates ________

via the _________ signaling pathway.

Answer 5

osteoclasts….NFkB

Question 6

What are 2 possible VIRAL etiologies for Paget disease? What does the association with rural living possibly suggest?

Answer 6

Paramyxovirus and measles…transmission of an infectious agent via contact with farm animals

Question 7

Paget disease may result from increased _______ receptor binding affinity among osteoclasts

Answer 7

vitamin D

Question 8

Pagets: increased osteoclastogenesis may be caused by hyperresponsiveness of osetoclast precursors to ______ and DECREASED INHIBITION of ______ signaling

Answer 8

RANKL (receptor activator of NFkB ligand)…RANK

Question 9

Paget disease of bone: age, gender?

Answer 9

Older pts (rare under 40yrs)…male

Question 10

Paget disease of bone: What serum test alerts the clinician?

Answer 10

alkaline phosphatase

Question 11

Paget disease of bone: 5 most common locations

Answer 11

1.pelvis 2.femur 3.lumbar vertebrae 4. Skull 5. tibia

Question 12

Paget disease of bone: buzzword for physical changes in weight-bearing bones

Answer 12

simian (monkeylike) stance

Question 13

Paget disease of bone: what % of pts experience JAW involvement? Mand vs max?

Answer 13

17%…2:1 maxilla:mand

Question 14

Paget disease of bone: what is the buzz word for the physical deformities if maxilla is severely affected?

Answer 14

lion-like (leontiasis ossea)

Question 15

Paget disease of bone: radiographically in EARLY stages, particularly in the skull there can be LARGE CIRCUMSCRIBED radiolucencies called __________

Answer 15

OSTEOPOROSIS CIRCUMSCRIPTA

Question 16

Paget disease of bone: radiographically in LATER stages, patches of sclerotic areas become confluent can appear as THIS BUZZ WORD _______

Answer 16

cotton wool

Question 17

Paget disease of bone: Generally the teeth can present with what anomaly?

Answer 17

hypercementosis

Question 18

Paget disease of bone can closely resemble WHAT other entitiy and thus a pt with this entity should be further evaluated to r/o Paget

Answer 18

CEMENTO-OSSEUS DYSPLASIA

Question 19

Paget disease of bone: Histologic BUZZWORD for pattern of bone

Answer 19

JIGSAW PUZZLE or MOSAIC (Basophilic reversal lines, which indicate the junction between alternating bone resorption and formation)

Question 20

Paget disease of bone: what are typical serum levels of alk phos, calcium, and phosphous?

Answer 20

elevated alk phos (exclue liver origin), normal calcium and phosphorous

Question 21

Paget disease of bone: symptomatic pts can be treated with…

Answer 21

bisphosphonates

Question 22

Paget disease of bone: dental complications - difficulties in extracting teeth with _________ and/or ankylosis; extensive hemorrhage from oral surgical procedures performed during the vascular _____ phase; and poor wound healing with increased susceptibility to osteomyelitis during the avascular ______ phase.

Answer 22

hypercementosis…lytic…sclerotic

Question 23

What is the % chance of Paget disease of bone progressing to osteosarcoma?

Answer 23

<1%

Question 24

A rare complication of Paget disease of bone (besides osteosarcoma) is the development of benign and malignant _________

Answer 24

giant cell tumor

Question 25

CGCG: age, gender, location

Answer 25

broad but 60% of cases below age 30, female, 70% in the mandible (ANTERIOR and CROSS THE MIDLINE)

Question 26

CGCG: Compared to non-aggressive lesions, aggressive lesions tend to be _____ at diagnosis, develop in somewhat _____ patients, and exhibit a greater ______ potential.

Answer 26

larger, younger,

Question 27

CGCG: Radiographically, the central giant cell granuloma
appears as a unilocular or multilocular radiolucency, with
well-delineated but _______ generally borders.

Answer 27

non-corticated

Question 28

CGCG: Small unilocular lesions may be confused with _______, and multilocular lesions may appear similar to _________.

Answer 28

periapical granulomas or cysts .. … ameloblastomas

Question 29

CGCG: Areas histopathologically identical to central giant cell granuloma have been noted in _________ and intermixed with _________.

Answer 29

aneurysmal bone cysts…central odontogenic fibromas

Question 30

CGCG: Because giant cell granulomas are also

histopathologically identical to __________, it should be ruled out in all instances.

Answer 30

brown tumors, hyperparathyroidism

Question 31

Multifocal giant cell lesions of the jaws may occur rarely as an isolated finding or in association with certain heritable conditions..name them (4)

Answer 31

1.Cherubism 2.Noonan-like/multiple giant cell lesion syndrome 3.Jaffe-Campanacci syndrome 4.Neurofibromatosis Type 1

Question 32

Microscopically, giant cell lesions of the jaws exhibit few to many multinucleated giant cells in a background of ovoid to spindle-shaped ___________ cells

Answer 32

mononuclear stromal

Question 33

CGCG: histology - which cell population is the proliferating component? What is the mechanism?

Answer 33

spindle cells…recruit moncyte-macrophage precursors and incudes differentiation into ostoclastic giant cells via RANK/RANKL pathway

Question 34

CGCG: The stroma may be loosely arranged and edematous or more cellular. Older lesions may show considerable stromal ______. Erythrocyte extravasation and hemosiderin deposition are often prominent. Focal bone or _______ formation may be present.

Answer 34

fibrosis…osteoid

Question 35

CGCG: first line tx curettage, what are the # alternate treatments?

Answer 35

1. intralesional corticosteroid injections 2.subcutaneous or nasal calcitonin 3. subcutaneous interferon alpha-2a, imatinib 4. bisphosphonates

Question 36

CGCG: there has been a WIDE range of recurrence rates reported (11-49%), but whats the settled upon #?

Answer 36

20%

Question 37

Giant Cell Tumor: Extragnathic giant cell tumors most often occur in the _______ of ________

Answer 37

epiphyses….long bones

Question 38

Compared to giant cell lesions of the jaws, extragnathic tumors are more likely to cause pain and tend to be diagnosed in patients who are 1 to 2 decades _____ on average, gender?

Answer 38

OLDER…NO gender predilection (unlike CGCG which favors females)

Question 39

In terms of biologic behavior, compared to jaw lesions, extragnathic Giant Cell lesions tend to be _______, with _____ recurrence rates after curettage.

Answer 39

more aggressive…higher

Question 40

Malignant degeneration of extragnathic Giant Cell lesions has been reported in 15% to 30% of true giant cell tumors, with ________ metastases in about 3% of extragnathic cases.

Answer 40

Pulmonary

Question 41

Some microscopic studies suggest that extragnathic giant cell tumors tend to exhibit more stromal ________ and larger, more uniformly distributed _________, with a greater number of nuclei.

Answer 41

cellularity……giant cells

Question 42

Cherubism: What type of inheritance pattern? Gender predilection??

Answer 42

AD, male (disputed)

Question 43

Cherubism: MOST cases are caused by WHAT TYPE of genetic mutation? WHAT GENE? Which chromosome?

Answer 43

Gain-of-function mutation…SH3BP2 gene on Chromosome 4p16

Question 44

Cherubism: Mutations lead to enhanced stability of the _____ adaptor protein and consequent upregulation of various signal transduction pathways resulting in hyperactive WHAT TYPE OF CELLS?

Answer 44

3BP2..osteoclasts

Question 45

Cherubism: What is another name for this? Why should it be avoided?

Answer 45

familial fibrous dysplasia..avoid because cherubism has NO relationship to fibrous dysplasia of bone

Question 46

Cherubism: when do the clinical alterations typically stabalize and slowly regress?

Answer 46

puberty

Question 47

Cherubism: besides the bony changes that cause the swollen appearance of the cheeks, what other phenomenon might be contributing to this appearance?

Answer 47

cervical lymphadenopathy

Question 48

Cherubism: if the inferior and lateral orbital walls are affected they might cause this buzzword/phrase..

Answer 48

“eyes upturned to heaven”

Question 49

Cherubism: what parts of the mandible are typically SPARED from being affected?

Answer 49

Condyles (angles, ascending rami, coronoid process usually affected)

Question 50

Cherubism: may cause what shape to the palate?

Answer 50

V shaped palatal arch

Question 51

Cherubism: is primarily limited to the craniofacial region, what other bones have been involved?

Answer 51

ribs

Question 52

Like the giant cells in central giant cell granulomas, the giant cells in cherubism express markers suggestive of WHAT CELL origin?

Answer 52

Osteoclastic

Question 53

Cherubism: Alternative treatment with ______ or _____ has been reported anecdotally but requires further study. Also, adalimumab (a ____ antagonist)—alone or in combination with ________—have yielded disappointing results thus far.

Answer 53

calcitonin or interferon…TNF-α..bisphosphonates

Question 54

Cherubism: Radiation therapy is CONTRAINDICATED because of the risk for ____________.

Answer 54

postirradiation sarcoma