5. Non-odontogenic Bone Pathology Flashcards
Central giant cell granuloma - non-\_\_\_\_ - most < \_\_\_\_; \_\_\_\_ > M - usually \_\_\_\_ - often extends \_\_\_\_; may cross \_\_\_\_
Central giant cell granuloma can be both well-defined or poorly-defined radiographically but are ALWAYS ____ (dark).
neoplastic 30 F MD anteriorly midline
CGCG
• This is a well-defined radiolucency with a sclerotic border (pink) but remember the border itself is not relevant per se, but what we are seeing again, a well-____ border.
• We are also seeing ____ of the roots, which it often presents as.
• A scalloping of the roots often indicates a traumatic bone cyst (which is technically not a cyst but rather a space
within the bone
◦ The space is thought to be resolved of some unresolved trauma
‣ Ie. A ____ within the jaw bone and as it resolved, the bone never filled in
• This kind of entity often manifests as a scalloped-type lucency
◦ Here, however, you have the same exact scalloped type lucency presentation, but this is NOT caused by a ____
◦ Thus, scalloping is not ____ for a traumatic bone cyst as it can occur in any context
defined scalloping hematoma trauma pathognomonic
Radiographically, poorly or well defined translucencies could both indicate ____. The nomenclature should seem familiar to us because we have heard it in peripheral giant cell granuloma, which is thought to have the same process of development as central giant cell granuloma (both are reactive lesions).
Key Differences: Peripheral Giant cell: ◦ Occurs in the \_\_\_\_ tissue ◦ Much more \_\_\_\_ Central giant cell granuloma ◦ occurs in the \_\_\_\_ bone
central giant cell granulomas
soft
common
jaw
BUT, the one in the jaw bone (central giant cell granuloma) can be locally ____ and can perforate the ____.
• Here is a young kid who had a lesion that perforated the jaw bone (near the maxillary canine and premolar).
• The same lesion has perforated the soft tissue
• However, this locally aggressive lesion is not unique to this entity (common to many different pathologies)
◦ Any mass-formed lesion in the jaw bone could disrupt local architecture
‣ Ie.Cause root resorption
‣ Tooth displacement
‣ Break through the bone
aggressively
root
• *____ is where you make the diagnoses in almost all of the central giant cell granuloma cases (99%).
• In this case, microscopically, it looks exactly the same as ____
• He can certainly ask us to recognize this on an exam** as we have had it in two contexts already
• Keys to look for:
◦ ____
◦ Multinucleate ____
◦ Extravasated ____
With only this picture, then we would think peripheral or central giant cell granuloma. The distinction would be if its peripherally-located in the gingiva or centrally-located within the jaw bone.
microscopically peripheral giant cell granuloma hemosiderin giant cells hemorrhage
Central hemangioma
Arterio-venous malformation
- 10 – 20 yrs; ____ > M
- ____:MX -> 2:1
- Uni- or ____ radiolucency
• As discussed in other lectures, hemangiomas are either ____ tissue tumors or tumors that occur within any ____ (mostly jaw). They can occur centrally.
• Because they occur centrally, any time you biopsy a lucency within any bone (even jaw bone), the clinician will invariably ____ the lesion first to make sure you are not dealing with a hemangioma
◦ Hemangiomas that occur within the jaw bone / any bone may look no different than any other more commonly occurring pathology.
F MD multilocular soft bone aspirate
Central hemangioma
Arterio-venous malformation
• Similarly, a large multilocular lesion occurring in this posterior mandible.. not that dissimilar from central giant cell granuloma or ameloblastoma (shown in last week’s lecture).
• Because you have no idea what you are dealing with and you can’t see color unless you perforate through the ____ (can’t see if red, blue, purple).
◦ Surgeons will stick a needle through the gum / bone into the lesion, aspirate and if they aspirate free flowing blood, they will stop and apply pressure. They will then send the pt to the hospital for a more controlled biopsy setting.
• Sometimes, as with the soft tissue or skin, we cannot tell if it is a true tumor or if it is an arterio-venous malformation (AVM).
The blood vessels may rewire themselves to give rise what we may commonly call ____ (typically AVMs)
For all intents and purposes, AVMs are no different than hemangiomas.
Both the demographics and appearances radiographically can relate to hemangiomas or AVMs.
bone
sturge-weber angiomatosis
Central hemangioma
Arterio-venous malformation
• When you biopsy, you can get ____ hemangioma, cavernous hemangioma, ____ hemangiomas
◦ Just like in soft tissues, the biopsy is based on what you see (caliber of blood vessels) microscopically.
capillary
venous
Radiolucency DD
Odontogenic \_\_\_\_ \_\_\_\_ \_\_\_\_ Central \_\_\_\_ Odontogenic \_\_\_\_
• Of this list of 5, Ameloblastomas & OKCs may or may not involve ____.
• Last week, he discussed how dentigerous cysts are found around the crowns of ____ teeth- so can ameloblastomas and OKCs
◦ Conversely Myxomas, hemangiomas, and Central giant cell granulomas are never found physically associated
with ____
◦ If you have an impacted tooth with a translucency around the crown of the tooth, it is NEVER going to be a
____, ____, or a ____
myxoma ameloblastoma central giant cell granuloma hemangioma keratocyst
teeth
impacted
tooth structure
myxomas
hemangiomas
central giant cell granuloma
Hyperparathyroidism (Brown tumor)
• May present with multiple jawbone lesions
• Histologically identical to ____
• Treat ____ source of disease
– Lesions may spontaneously ____
One of the more common things being Hyperparathyroidism.
• Where have we learned about this disorder (secondary parathyroidism)?
Ans: ____. In chronic renal failure, patients will have secondary parathyroidism. But there is a primary form as well that we will learn in BS.
• Secondary or primary parathyroidism may manifest with jawbone lesions
◦ Radiographically ____
◦ Oftentimes ____, distinct multiple lesions
◦ Often in the ____ (although sometimes in the long bones)
◦ Microscopically, these lesions look no different than central giant cell granulomas except these are ____
CGCG
primary
resolve
kidney
lucent
jawbone
multifocal
Primary hyperparathyroidism
• Excessive PTH from parathyroids
• Caused by
– Parathyroid ____
– Parathyroid ____
– Parathyroid ____ of all four glands
• If it is caused by a primary hyperparathyroidism (in the parathyroid gland) you have to resolve the primary pathology in that gland
• As with the pituitary gland pathology (cushing’s where tumor expresses ACTH), if a tumor in the parathyroid gland is expressing PTH at high levels, that will cause ____ hyperthyroidism
• In secondary hyperparathyroidism, the ____ is malfunctioning
◦ Normally, the kidney regulates Vitamin D metabolism, CaPO4.
◦ When not functioning, the kidney triggers excessive ____ release from the parathyroid gland
adenoma
carcinoma
hyperplasia
primary
kidney
PTH
Secondary hyperparathyroidism
Chronic ____ failure
Severe ____
____ deficiency
Any of these three could cause a secondary hyperparathyroidism
• This is a systemic disease but the bone lesions are highly characteristic
◦ If you have ____, ____ lesions, that is Pathognomonic for hyperparathyroidism (cannot tell if it is primary or secondary) so you must figure out for yourself.
renal hypocalcemia vitamin D multifocal central giant cell
Hyperparathyroidism
• You can treat the primary disease and the lesions may ____ on their own without any surgical intervention
◦ Interestingly, these lesions are reactive again, can also be treated by an intralesional ____ injection. Rather than surgically excising multiple lesions, they can be injected with a steroid and that can help resolve a lesion.
resolve
steroid
Cherubism
• Autosomal ____ disease – 4p16, ____ gene
• Usually ____, symmetric jaw expansion
• Early onset, spontaneous resolution by ____
• Histologically similar to ____
– ____ cuffing
• In contrast, cherubism is a genetic disease
◦ Characterized by a typically bilateral, ____ jaw expansion
◦ Less commonly all 4 quadrants could be affected
◦ This disease gets its name from when as the maxilla expands, the sclera (whites of the eye) become so
prominent to the point of appearing like these patients are looking up at the sky
• This disease is both a genetic disease and self-limiting
• When kids reach puberty, the growth will stop ____ and some surgery may be required to return them to a
more aesthetic state.
• Microscropically very similar to central giant cell granulomas
dominant SH3BP2 bilateral puberty CGCG eosinophilic perivascular symmetric spontaneously
Cherubism
• This patient has 2 large multilocular lesions in her mandible (her ____ was not impacted)
maxilla
Cherubism
• Another patient who has two multilocular translucent lesions in the mandible with an unaffected maxilla
• We can see first molars that are unerupted so the patient’s age is about 4.
• Microscopically, these also look like giant cell lesions with one exception
◦ The Exception is ____ (pathognomonic for Cherubism)
◦ Cuff of eosinophilic material (collagen) around the blood vessels
perivascular eosinophilic cuffing
Cherubism
Histology recap for Cherubism:
- ____
- ____
- Extravasated ____
- ____
• In a young patient with multilocular translucent lesions in all 4 quadrants, it is Cherubism until proven otherwise
• If you see ____ lesions in the posterior mandible, it is Cherubism until proven otherwise
• If you see a ____ lesion, it is NOT cherubism until you investigate further. This may be something else (but it can
still be cherubism)
◦ All must be confirmed with biopsy
• Patients here because of their young age and not wanting to disrupt their growth through surgery, are treated with intralesional ____ in attempt to reduce the size
◦ Once the lesions stop growing (post-puberty), surgeons will go in and ____ the bone
hemosiderin
giant cells
blood
perivascular eosinophilic cuffing
bilateral
single
steroids
recontour
Aneurysmal bone cyst
• True \_\_\_\_ tumor • t(16;17)(q22;p13) – \_\_\_\_ fusion oncogene • \_\_\_\_ > M, 70% < \_\_\_\_ years • \_\_\_\_:MX, 2:1
-Last but not least, in the lesions that look like giant cell lesions microscopically is an aneurysmal bone cyst (ABC):
◦ NOT a ____ (misnomer) as it is a true benign tumor.
‣ The other things we have talked about have not been tumors but reactive
◦ Produced by a reproducible (recurrent) chromosomal ____ resulting in overexpression of the proto-oncogene called USP6 (studied at CHOP).
• Radiographically, the lesions look like anything else as it can be:
◦ Unilocular
◦ Multilocular
◦ ALWAYS ____
• Intriguingly, this tumor has a very striking female predilection and has a high predilection for the mandible (occurs
mostly in the jaw bone)
• Also occurs more so in younger people than older people. However, it is not to say this is a pediatric tumor
benign USP6 F 20 2
cyst
translocation
radiolucent`
Aneurysmal bone cyst
• Radiograph – \_\_\_\_, posterior MD • Microscopic appearance – \_\_\_\_ spaces – \_\_\_\_ (resembles CGCG)
• What is important about this tumor is that it contains LOTS of blood, but is not a ____ tumor (not a hemangioma)
◦ Blood in this ABC tumor is ____ (not intravascular like a hemangioma).
◦ When you take out this tumor in its entirety, it looks like a blood filled sponge (you could squeeze the blood out
of it….)
• In this anatomically gross depiction, you can see a lot of spaces that are in fact spaces and not blood vessels.
◦ The kind of sinusoidal spaces you see in kidney aren’t lined by endothelium but are containing blood
• An aspiration will reveal blood but NOT ____ blood which will speak to this not being a hemangioma / AVM
◦ However still get blood because it is a blood filled mass
• Microscopically, this resembles a giant cell granuloma EXCEPT
◦ Large areas filled with blood (appear pink in histology see slide below)
(Comes back to this slide later on to say the following)
• These tumors can be locally ____ masses so it requires a local resection much like an ameloblastoma which
requires you to remove it in its ____.
multilocular
sinusoidal
multinucleated giant cells
vascular
extravasated
aggressive
entirety
ABC
◦ Appears like CGCG, with the addition of spaces that are all filled with ____ (dark pink). This is an ABC, which again is not a true cyst but rather a ____
blood
benign tumor
Benign fibro-osseous lesions
Diverse group of pathologic conditions I – \_\_\_\_ lesions 3 – \_\_\_\_ or “dysplastic” diseases z – \_\_\_\_ Histologic similarities Important to subclassify – Therapeutic management varies
- fibrous dysplasia
- ____
- ____
- ____
- – mccune-albright syndrome
• 2 Ossifying fibroma • \_\_\_\_-Jaw tumor syndrome • 3 Osseous (cemento-osseous) dysplasia – \_\_\_\_ – Focal – \_\_\_\_
• All characterized similarly despite different etiologies because histologically they may look the exact same.
• Diagnosis requires not only histology, but also in some cases ____ information
◦ Age / race could be important
• What defines pathology is ____ combined with ____ combined with the patient’s ____
developmental
reactive
neoplasms
monostotic
craniofacial
polyostotic
hyperparathyroidism
periapical
florid
demograph
histology
radiology
demographics
Disorder of stem cell differentiation: Fibrous dysplasia
- Somatic mutation in ____ gene – Gsα protein coupled receptor
- Results in overproduction of cAMP with activation of ____
- Prevents transition of bone-forming progenitor cells to ____ osteogenic cells
Fibrous dysplasia is a disorder of ____l differentiation
• •
•
Not a genetic disease, but has a genetic basis
Post-zygomatic or a somatic disease: gene defect occurs early during ____ development or later during fetal development, resulting in overactivation in an important G-protein coupled receptor
◦ The gene is called GNAS, which expresses a protein that is a ____ subunit of a G protein receptor
◦ G-proteins are membrane proteins that signal through cyclic AMP and protein kinase C. Through its
signaling cascade will activate a bunch of other proteins that then regulate a lot of biological processes.
When this GNAS mutation occurs, it results in overactivation of the G-protein which in turn results in constitutive stimulation of cAMP, which will activate an array of downstream processes, most importantly activation of the proto-oncogene named c-FOS
◦ These patients may develop some tumors elsewhere in the ____ beyond just in the jaw bone.
GNAS
c-FOS
mature
stem cell
embryonic
stimulatory
body
Disorder of stem cell differentiation: Fibrous dysplasia
•
In a normal physiology, this protein cascade helps to differentiate progenitor bone stem cells into mature osteogenic cells (bone-producing cells)
◦ When this mutation occurs, that transition does not occur properly
◦ Depending on how early this mutation develops (early in the embryo or later in development) will dictate
which tissues and how many tissues are effected in one of these patients
‣ If very early in development, the patient will have very prominent disease effecting ____ tissues not just bone
• When it effects multiple tissues, we call it ____ syndrome
‣ If occurs much later in development (for example after birth or even later), chances are it is limited to ____ bone at most.
• When it effects just one bone, that is what we describe as fibrous dysplasia
several
mccune-albright
one
Fibrous dysplasia
• When it occurs in the jaw bones as fibrous dysplasia, most commonly it occurs in the ____ as a ____, expansile growth of a bone.
maxilla
unilateral
Fibrous dysplasia
• \_\_\_\_ or polyostotic • \_\_\_\_ or mandibular involvement – 25% of all FD – 35% of patients with MAS • “Craniofacial FD” used to describe FD of \_\_\_\_ bone • Almost always a \_\_\_\_ disease
• This is a different patient who also had this growth in the maxilla
• If it is single bone affected, we call it ____ fibrous dysplasia
◦ Of all patients who have this monostotic disease (single bone), 25% will have ____ involvement either maxillary or mandibular
• If multiple bone affected, it is ____ FD
◦ When polyostotic, typically also have different parts of the body effected. These patients are typically McCune
Albright syndrome
◦ Of all patients who have this systemic disease, 35% of patients will have ____ disease
monostotic
maxillary
maxillary
unilateral
monostotic
craniofacial
polyostotic
maxillo-facial
Fibrous dysplasia
• 1st or 2nd decades
• ____-growing, painless expansion
– Facial ____
– Occasionally expansion may be ____ or accelerate after period of slow growth
• Fibrous dysplasia occurs in young people, as it is a ____ or a young person disease. It does not manifest as a primary disease after the age of 20 perhaps.
• If it is a patient over the age of 20, it is not this ____ by definition
• Typical manifestation is slow growing, unilaterally expanding:
◦ With or without ____ of the adjacent teeth
◦ With or without any changes to facial symmetry, depending on how large it gets
◦ Importantly, these patients may have slow growth for days and then one day they realize oh my gosh its growing much larger/more quickly
‣ This is a BAD sign as it is a sign of FD becoming more ____ (potentially development of ____ within the effected bone)
‣ FD predisposes a patient to ____
slow
asymmetry
rapid
pediatric disease movement significant cancer malignancy
