Ch14 Bone Path (Part II) Flashcards
What is the other name for PAGET Disease of bone?
OSTEITIS DEFORMANS
Name that bone pathology: is characterized by abnormal, anarchic resorption and deposition of bone, resulting in skeletal distortion and weakening
Paget Disease of Bone
What is the 2nd most common metabolic bone disorder behind osteoporosis?
Paget Disease of bone
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?
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
Mechanism of Paget: SQSTM1 activates ________
via the _________ signaling pathway.
osteoclasts….NFkB
What are 2 possible VIRAL etiologies for Paget disease? What does the association with rural living possibly suggest?
Paramyxovirus and measles…transmission of an infectious agent via contact with farm animals
Paget disease may result from increased _______ receptor binding affinity among osteoclasts
vitamin D
Pagets: increased osteoclastogenesis may be caused by hyperresponsiveness of osetoclast precursors to ______ and DECREASED INHIBITION of ______ signaling
RANKL (receptor activator of NFkB ligand)…RANK
Paget disease of bone: age, gender?
Older pts (rare under 40yrs)…male
Paget disease of bone: What serum test alerts the clinician?
alkaline phosphatase
Paget disease of bone: 5 most common locations
1.pelvis 2.femur 3.lumbar vertebrae 4. Skull 5. tibia
Paget disease of bone: buzzword for physical changes in weight-bearing bones
simian (monkeylike) stance
Paget disease of bone: what % of pts experience JAW involvement? Mand vs max?
17%…2:1 maxilla:mand
Paget disease of bone: what is the buzz word for the physical deformities if maxilla is severely affected?
lion-like (leontiasis ossea)
Paget disease of bone: radiographically in EARLY stages, particularly in the skull there can be LARGE CIRCUMSCRIBED radiolucencies called __________
OSTEOPOROSIS CIRCUMSCRIPTA
Paget disease of bone: radiographically in LATER stages, patches of sclerotic areas become confluent can appear as THIS BUZZ WORD _______
cotton wool
Paget disease of bone: Generally the teeth can present with what anomaly?
hypercementosis
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
CEMENTO-OSSEUS DYSPLASIA
Paget disease of bone: Histologic BUZZWORD for pattern of bone
JIGSAW PUZZLE or MOSAIC (Basophilic reversal lines, which indicate the junction between alternating bone resorption and formation)
Paget disease of bone: what are typical serum levels of alk phos, calcium, and phosphous?
elevated alk phos (exclue liver origin), normal calcium and phosphorous
Paget disease of bone: symptomatic pts can be treated with…
bisphosphonates
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.
hypercementosis…lytic…sclerotic
What is the % chance of Paget disease of bone progressing to osteosarcoma?
<1%
A rare complication of Paget disease of bone (besides osteosarcoma) is the development of benign and malignant _________
giant cell tumor
CGCG: age, gender, location
broad but 60% of cases below age 30, female, 70% in the mandible (ANTERIOR and CROSS THE MIDLINE)
CGCG: Compared to non-aggressive lesions, aggressive lesions tend to be _____ at diagnosis, develop in somewhat _____ patients, and exhibit a greater ______ potential.
larger, younger,
CGCG: Radiographically, the central giant cell granuloma
appears as a unilocular or multilocular radiolucency, with
well-delineated but _______ generally borders.
non-corticated
CGCG: Small unilocular lesions may be confused with _______, and multilocular lesions may appear similar to _________.
periapical granulomas or cysts .. … ameloblastomas
CGCG: Areas histopathologically identical to central giant cell granuloma have been noted in _________ and intermixed with _________.
aneurysmal bone cysts…central odontogenic fibromas
CGCG: Because giant cell granulomas are also
histopathologically identical to __________, it should be ruled out in all instances.
brown tumors, hyperparathyroidism
Multifocal giant cell lesions of the jaws may occur rarely as an isolated finding or in association with certain heritable conditions..name them (4)
1.Cherubism 2.Noonan-like/multiple giant cell lesion syndrome 3.Jaffe-Campanacci syndrome 4.Neurofibromatosis Type 1
Microscopically, giant cell lesions of the jaws exhibit few to many multinucleated giant cells in a background of ovoid to spindle-shaped ___________ cells
mononuclear stromal
CGCG: histology - which cell population is the proliferating component? What is the mechanism?
spindle cells…recruit moncyte-macrophage precursors and incudes differentiation into ostoclastic giant cells via RANK/RANKL pathway
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.
fibrosis…osteoid
CGCG: first line tx curettage, what are the # alternate treatments?
- intralesional corticosteroid injections 2.subcutaneous or nasal calcitonin 3. subcutaneous interferon alpha-2a, imatinib 4. bisphosphonates
CGCG: there has been a WIDE range of recurrence rates reported (11-49%), but whats the settled upon #?
20%
Giant Cell Tumor: Extragnathic giant cell tumors most often occur in the _______ of ________
epiphyses….long bones
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?
OLDER…NO gender predilection (unlike CGCG which favors females)
In terms of biologic behavior, compared to jaw lesions, extragnathic Giant Cell lesions tend to be _______, with _____ recurrence rates after curettage.
more aggressive…higher
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.
Pulmonary
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.
cellularity……giant cells
Cherubism: What type of inheritance pattern? Gender predilection??
AD, male (disputed)
Cherubism: MOST cases are caused by WHAT TYPE of genetic mutation? WHAT GENE? Which chromosome?
Gain-of-function mutation…SH3BP2 gene on Chromosome 4p16
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?
3BP2..osteoclasts
Cherubism: What is another name for this? Why should it be avoided?
familial fibrous dysplasia..avoid because cherubism has NO relationship to fibrous dysplasia of bone
Cherubism: when do the clinical alterations typically stabalize and slowly regress?
puberty
Cherubism: besides the bony changes that cause the swollen appearance of the cheeks, what other phenomenon might be contributing to this appearance?
cervical lymphadenopathy
Cherubism: if the inferior and lateral orbital walls are affected they might cause this buzzword/phrase..
“eyes upturned to heaven”
Cherubism: what parts of the mandible are typically SPARED from being affected?
Condyles (angles, ascending rami, coronoid process usually affected)
Cherubism: may cause what shape to the palate?
V shaped palatal arch
Cherubism: is primarily limited to the craniofacial region, what other bones have been involved?
ribs
Like the giant cells in central giant cell granulomas, the giant cells in cherubism express markers suggestive of WHAT CELL origin?
Osteoclastic
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.
calcitonin or interferon…TNF-α..bisphosphonates
Cherubism: Radiation therapy is CONTRAINDICATED because of the risk for ____________.
postirradiation sarcoma
