Pathology - Angelfire



Pathology- Dr Graham A Cauchi/Hewitt Joint

9 Mar 2001, 11a.m

Bone and Joint Disorders

This scribe is everything Dr. Graham said, whether it is in the slides or not. It wouldn’t hurt to follow along on pages 435-436 in the notes. Her slides were on a carousel therefore cannot be put on the web so when possible, I will reference pictures from one of three sources: WP = Web path, C= Curran’s atlas, R= Robbins.

Osteogenesis Imperfecta (quick summary from last hour)

o Things to remember: Pathological fractures, wormian bones, and various manifestations from intrauterine death to long life. Scribe note: Can also lead to delusions of being a supervillain (Unbreakable, anyone?).

Fibrous Dysplasia (FD)

o If osteogenesis imperfecta is a problem with one point mutation and problems in type I collagen, fibrous dysplasia is much more uncertain. In fact, we don’t know why it happens.

o It is not a generalized disease (doesn’t involve every bone in the body) but it can affect one bone (monostotic disease) or it can affect more than one bone (polyostotic disease).

o When it affects multiple bones, it tends to attack only one half of the body. Reason unknown.

o Final result is poor bone formation

❖ Instead of a meshwork of cancellous or spongy bone with intervening fat or hematopoeitic marrow and blood vessels, you end up with bone that is meshed with fibrous tissue.

❖ Instead of giving the appearance of bone being formed from osteoblasts, you get the impression that it arose from “primordial murk”. This means that small spicules of bone are scattered about in a sea of fibrous tissue without osteoblasts surrounding them.

o Subject to pathological fracture.

o Ground glass appearance on radiograph- dark and hazy on x-ray (grayish).

o Shepherd’s crook deformity (buzzword). A deformity of the proximal femur that gives the bone the shape of the top of a shepherd’s crook. Multiple episodes of fracture followed by healing of the proximal femur will result in this deformity. This also results in an abnormality in the hip joint.

o Histo(R 28-35, C 3.3) : The center part of bone should have spongy spicules that look similar to what we see in these two pictures, but look how they are surrounded by nothing but fibrous tissue. Osteoblasts should surround these spicules.

❖ Higher power (No example): The fibrous tissue is perfectly benign looking. The spicules, however, are not lined by osteoblasts, as they should be. The spicules sort of look like Chinese letters (talk to Flying Cougar Kuo or Iron Eagle Wang if you don’t know what these look like).

o Clinical presentation

❖ 70% of FD is monostotic. These often mimic bone tumors.

❖ 27% of FD is polyostotic.

❖ The remaining 3% includes polyostotic disease associated with endocrine abnormalities, in this case, Albright’s syndrome. “There is more about that in your book but you will learn about that later.” Here is a quick summary of it taken from checkerboard (P340): Polyostotic fibrous dysplasia, precocious puberty, café-au-lait spots on skin, and short stature. Occurs in very young girls.

❖ Case slide: Rib with a huge end to it. There are very few primary bone tumors that affect ribs; one being an enchondroma (extra cartilage that looks like a lump in a rib), and the other being fibrous dysplasia. Can also present as a pathological fracture of a rib.

❖ Slide: Tibia and fibula. Looks like a hole in the tibia. Look at the fibula with it- its edges are very irregular, with radiolucent areas as well. Since you have two bones affected, you can pretty much rule out a primary bone tumor because that usually affects one spot on one bone. Cool side note: Metastases to bone usually occur above the knees and above the elbows, so this is unlikely to be a metastatic lesion.

❖ FD frequently involves the skull, especially in polyostotic disease. One of the major causes of skull abnormalities in children and adolescents. So, if someone comes in with unilateral proptosis (eye moving out to the side of the face), or malformation of the cheekbones, think fibrous dysplasia especially if it an adolescent. The two ways to deal with FD are to either live with the deformity, which is pretty horrible, or to take it out and live with the malformation. Remember, this is benign and will eventually “burn itself out”. (Slide:skull that looked like a stone mask)

o Age or presentation

❖ Present from the early years so it will affect older children vs. something that will affect adults.

❖ FD presents in multiple bones, which is a key way to differentiate it as the cause of pathological fracture.

Osteoporosis

o Most common bone disease that we will encounter. It is a metabolic bone disease.

o Definition of osteoporosis: reduction in the quantity of bone

o Definition of osteopenia: decreased calcification or density of bone (as seen on radiograph).

o Anyone who has fractured a bone and hasn’t used it for a length of time and has then seen an x-ray of that bone will notice that it is paler than normal. The body says “Hey, why the heck am I wasting energy mineralizing this stupid bone if this yahoo isn’t gonna use it?” (which, along with ‘I’m Just a Bill’ was my favorite Saturday morning Schoolhouse Rock song.) This results in the dumping of calcium into the blood; this will continue until use of the extremity begins again.

o Over time, formation can’t keep up with breakdown of bone. Instead of being able to make more bone to respond to the bone breakdown, you can’t keep up with the demand. This results in bone mass decreasing starting at around age 35.

❖ This is why doctors urge people to keep active and eat healthily.

o Note: The bone is mineralizing just as it should be. There is no problem in that area. The problem lies in the fact that you just aren’t making enough bone. This makes it look “thin” and osteopenic on radiograph.

❖ Osteomalacia: When you have the correct amount of bone mass, but it isn’t mineralizing. So this dz will also look “thin” on radiograph.

o Histo (C 3-15) NOTE: Web path has an osteoporosis tutorial at the top of the bone and joint page that has many similar slides. For this specific slide preparation the pathologist uses demineralized bone, which takes about a month to do. Take a punch biopsy of the iliac wing so you can see both sides. Everything that is mineralized is stained black (spicules). There are many spicules and most are connected to each other. If you then look at a bone from someone with osteoporosis, you can see that the spicules are thin and scrawny, they don’t touch each other, and the cortex is even degraded. Why is this happening? In the osteoclast vs. osteoblast battle, the osteoclasts are winning (Like the Red Wings vs. the Stars)

o The first bones to fracture are those with a thin cortex and a core of trabecular meshwork. Usual locations for initial sx: distal ulna and radius and vertebral bodies (R 28-9). Very painful, women can lose up to six inches in height!

o Types of osteoporosis

❖ Postmenopausal: Big problem for post menopausal women who are not on estrogen replacement therapy

❖ Senile (No longer a PC term- see “The Big Lebowski” for a great explanation of a PC term, Duderama). Simply means that it happens later in life, around the 7th or 8th decade. By this time, the dz has even had an effect on the cortex of the bone and this is when we start to see some fractures (femoral neck). Happens to both sexes but more in women.

o Lab

❖ Serum calcium, phosphorous, alk. phosphatase: ALL NORMAL.

o X-ray

❖ Thin, skinny bones.

o Tx

❖ We have been trying a number of things to treat and prevent the disease: ‘ poisoning’ osteoclasts and giving estrogen after menopause to maintain the formation of bone.

❖ We can’t really treat osteoporosis. What we do, though, is evaluate the patient for other disorders that we can treat that could be causing these problems, like cancer. No matter what, we simply need to rule out cancer in our differential. Other examples of treatable causes that we need to rule out include hyperparathyroidism and rheumatoid arthritis. Certain drugs can also cause similar bone patterns.

o Figure 28-8, page 1223. The pathophys of osteoporosis. She said to look at it but she wasn’t going to go over it in class.

Osteopetrosis

o Very rare generalized dz of having too much bone, which results from defective osteoclast function.

o The primary problem is that you cannot break down mineralized bone or the cartilage spicules that are the precursor to bone. This results in several problems (only 3 mentioned in lecture):

❖ The bone is so disorganized in its calcification that pathological fractures occur.

❖ The excessive amount of poorly organized bone leads to a loss of trabecular space. Eventually, the loss of space is so drastic that the marrow no longer has any room and hematopoeisis must occur in extramedullary spaces.

❖ Can result in impingement of cranial nerves due to a thickening of the skull; this can even produce deafness.

o Slide: (R 28-10) Not just an overexposed radiograph – look at how dense the bone is. This is a child, which is why there are the epiphyseal gaps between the bones. The bone is very brittle, even chalk-like.

Paget’s disease of bone (osteitis deformans)

o This is something we will encounter because it is relatively common.

o It can be either monostotic or polyostotic. Bone is subject to pathological fracture.

o Pathogenesis

❖ Uncontrolled bone turnover driven by osteoclasts. It is normal bone remodeling but at an accelerated rate.

❖ Normal calcium and phosphorus metabolism, but you have a high ALK PHOS. This can be fractionated to determine if it is from bone. You can get very high levels due to this disease (20,000).

❖ Most affects the axial skeleton including the skull and proximal femur.

❖ Etiology really unknown. Hypothesized that there is a paramyxovirus inclusion in the osteoclasts; measles virus transcripts have been implicated, but no one is certain. This does appear to be an acquired disease.

❖ There is one family that could show that Paget is a heritable disease on chromosome 18. This is still under investigation. There is also a group of persons with Paget dz in a town in Italy. These persons end up with a benign giant cell tumor. (Fascinating huh? Kinda like Kuru, you know, that prion disease – hey, that’s what she said)

❖ Because you are remodeling so much bone, you often end up with larger, coarser bones.

❖ Can end up with bone bowing and pain and even osteoarthritis.

❖ Only 1% of persons with Paget’s dz will end up with a secondary sarcoma. Osteosarcoma as a secondary tumor in the elderly is fatal within one year.

❖ Don’t worry about the GC (giant cell) tumor.

o Stages

❖ Early: osteoclasts eat up bone- if there is too little bone left, fractures will easily occur.

❖ Mid: healing of the fractured bone. Still a chance of fracture.

❖ End: “mish-mash” of bone is present but now it is very poorly put together so it is subject to pathological fracture.

• BUZZWORD: Seen in the late stage: Mosaic bone.

o Slides (R 28-13, 14; C 3.13; W 34-35) Not all of the slides discussed could be found in the books or on the web.

❖ Every time you stop and start making bone, you end up with a cement line (C3.13, thin arrow). This is a bit of phosphate and residual junk that stained blue. It shows where bone repair stopped and started.

❖ Osteoclasts are usually seen breaking down the bone.

❖ Osteoblasts shown laying down collagen that will eventually become bone. This bone is being laid down quickly and very sporadically; thus it is weaker than normal bone. It will mineralize as it should but because it is not being laid down in a nice lamellar fashion, it will be much weaker.

❖ Paget’s dz of the skull. Patches of light and dark spots on the bone. Think of a wave of osteoclasts starting at one end of the skull, moving across it and eating bone as they go. Behind them, you will have osteoblasts reforming bone. This is why there are concurrent areas of mineralized bone and demineralized bone in the skull.

• Will result in thickening of the bone. Speculated that this is why Beethoven was deaf.

❖ X-ray: Thoracic spine. One of the vertebral bodies is very white (mineralized). Men who have prostate cancer can have metastasis to the vertebral bodies in the form of an osteoblastic metastasis. (Paget’s dz is in the differential for some malignant diseases)

❖ Vertebral bodies: cannot differentiate between the cortex and trabecular meshwork.

o Very vascular.

❖ With the increased blood flow to the bones needed for all of this reconstruction, someone can actually develop high output heart failure. “like being pregnant in your bones”

❖ If patients are older and already in failure, Paget’s can severely worsen it.

❖ If you fracture through these, it is very bloody. The patient loses a ton of blood because of the damage to the vascular structures.

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