BONES AND SOFT TISSUES
Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com

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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.

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Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

Our world is full of people who have found peace, fulfillment, and friendship by suspending their own reasoning and simply accepting a single authority that seems wise and good. I've learned that they leave the movements when, and only when, they discover they have been maliciously deceived. In the meantime, nothing that I can say or do will convince such people that I am a decent human being. I no longer answer my crank mail.

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Preventing "F"'s: For Teachers!

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Courtesy of CancerWEB


It is difficult to imagine the "politically correct" revision of Victor Hugo's work as "The Angular Kyphotic of Notre Dame".

KCUMB Students
"Big Robbins" -- Bones / Joints / Soft Tissue Tumors
Lectures follow Textbook

QUIZBANK

Musculoskeletal
Taiwanese pathology site
Good place to go to practice

Bone, Joint, Soft Tissue
Photo Library of Pathology
U. of Tokushima

Soft Tissue
Surgical Pathology Atlas
Nice photos, hard-core

Bone and Cartilage
Surgical Pathology Atlas
Nice photos, hard-core

Musculoskeletal
Utah cases for path students
Juliana Szakacs MD

Bone Slides
Iowa Virtual Microscopy
Have fun

Musculoskeletal
Photos, explanations, and quiz
Indiana U.

Bone and Joints
Brown Digital Pathology
Some nice cases

Non-Neoplastic Bone
From Chile
In Spanish

Bone Pathology
Photomicrograph collection
In Portuguese

Bone Tumors I
From Chile
In Spanish

Bone Tumors II
From Chile
In Spanish

Bone Tumors III
From Chile
In Spanish

Bone Tumors IV
From Chile
In Spanish

Clinical Musculoskeletal Pathology
Go through IMC
You need to join first.

Bone Exhibit
Virtual Pathology Museum
University of Connecticut

Fetal growth plate
WebPath Tutorial -- comments are down right now

Osteoblasts
WebPath Tutorial -- comments are down right now

Woven bone
WebPath Tutorial -- comments are down right now

Cancellous (lamellar) bone
Polarized light
WebPath Tutorial -- comments are down right now

{14645} osteoblasts, normal
{46508} osteoclasts, normal
{14647} osteoclasts, normal

INTRODUCING BONE

    You know bone supports you, protects you, and stores your calcium and phosphorus. You know osteoblasts in their rows making the super-densely-woven collagen that is osteoid, osteocytes in their lacunes (hard to study, but not inert), multinucleated (usually; 3-20 nuclei) osteoclasts with ruffled contact surfaces in their Howship's lacunes / resorption pits / resorption bays, compact cortical bone, spongy cancellous bone, the flat endosteal cells that line bone (osteoblasts that did not become osteocytes), and so forth. You know that bone perennially remodels itself. (This is why the orthodontist can straighten teeth, and how you replace your entire skeleton each decade.) You also know that unmineralized bone is called OSTEOID, which is mostly densely-woven type I collagen, with some vitamin K dependent calcium-binding proteins mixed in.

Hyperparathyroid bone disease
Many osteoclasts
KU Collection

Brown tumor
WebPath Tutorial -- comments are down right now

Brown tumor
WebPath Tutorial -- comments are down right now

{18649} polydactyly

FRACTURE TERMS

{07029} healing fracture, histology
{08994} healing fracture, histology

Healing fracture
WebPath Tutorial -- comments are down right now

Healing fracture
WebPath Tutorial -- comments are down right now

OSTEOGENESIS IMPERFECTA ("brittle bone diseases", * fragilitas ossium; Clin. Ortho. 401: 6, 2002; Lancet 363: 1377, 2004)

{12402} osteogenesis imperfecta
{15795} osteogenesis imperfecta, blue sclera
{18255} osteogenesis imperfecta type II
{15801} osteogenesis imperfecta type II
{18256} osteogenesis imperfecta, x-ray
{15813} osteogenesis imperfecta, sutures not present

"Unbreakable" increased public awareness
of osteogenesis imperfecta. Mr. Jackson
is rather tall to be an OI patient.

Osteogenesis imperfecta
X-rays from Harvard

OSTEOPETROSIS ("marble bones", "Albers-Schonberg disease"; Am. Fam. Phy. 57: 1293, 1998)

Osteopetrosis
Skull x-ray

ACHONDROPLASIA (Lancet 370: 162, 2007; Arch. Dis. Child. 97: 129, 2012 especially for the new surgical options)

    An autosomal dominant condition (often a new mutation) in which there is impaired formation of the long bones by the familiar endochondral process. The limb bones are short, with abnormally wide ends. The patient has a head and trunk of normal size, and disproportionately short but well-muscled arms and legs. The face usually has a large forehead, prominent supraorbital ridges, and deepset root of the nose (looks like a very mild Apert's). Sexuality is generally normal, and intelligence is distributed as for the general population, with many well above-average (Am. J. Med. Genet. 41: 208, 1991).

Portrait of the entertainer Sebastian de Morra by Velazquez

Don Sebastian de Morra, by Velazquez

{25610} achondroplasia
{25688} achondroplasia
{49474} "achondroplasia" (looks like a thanatophoric dwarf to me, failure of rib development)

Little People of America
Good resources

Achondroplastic dwarf

KU Collection

Achondroplasia
Famous surgeon at the Hop
Nice essay too

{53757} Apert's
{53760} Apert's

* PYCNODYSOSTOSIS
    There seems to be a consensus today that artist Henri de Toulouse-Lautrec's dwarfism and deformities were caused by PYCNODYSOSTOSIS.

    Here is the evidence:

    • He had fragile bones and sustained fractures as a young teen from minor trauma.

    • His facial features were considered bizarre ("cute") from his babyhood. He had an extremely small chin, which he concealed by a beard.

    • His fontanelle never closed. He protected his head by almost always wearing a hat.

    • His fingers were very short, especially at the tips.

    • His parents were first cousins.

    All this fits with pycnodysostosis and probably nothing else. Making the call: JAMA 191: 111, 1965; more recently Nat. Genet. 10: 128, 1995. This is an autosomal recessive illness caused (at least sometimes) by defective cathepsin K, found only in osteoclasts and responsible for removing bone matrix (J. Clin. Endo. Metab. 85: 425, 2000); the bones are demineralized normally by osteoclasts but they cannot take out the collagen fibers. It's not clear exactly how the phenotype is produced. Pathology J. Clin. Endo. Metab. 89: 1538, 2004.

Toulouse-Lautrec
Henri de Toulouse-Lautrec

* OTHER GENETIC SYNDROMES

Fibrodysplasia ossificans progressiva
25 year old man
From NEJM

Fibrodysplasia ossificans progressiva
Six year old girl
From Kaplan JBJSA 75A

BONE INFARCTS

PYOGENIC OSTEOMYELITIS (Lancet 364: 369, 2004)

{05293} osteomyelitis, x-ray (see it? areas of dead bone often end up mottled-radiodense)
{39505} osteomyelitis, x-ray
{40090} osteomyelitis, draining sinus

Osteomyelitis
Pittsburgh Pathology Cases

Osteomyelitis
Pittsburgh Pathology Cases

Healing osteomyelitis
WebPath Tutorial -- comments are down right now

Osteomyelitis
Pittsburgh Illustrated Case

SYPHILIS was famous for producing gummas and periostitis, and Shakespeare even calls it "the Neapolitan bone-ache."

Syphilitic periostitis, skull
Classic photo
Adami & McCrae, 1914

TUBERCULOUS OSTEOMYELITIS

OSTEOPOROSIS (Ann. Int. Med. 126: 458, 1997; Med. Clin. N.A 87: 1039, 2003; J. Clin. Inv. 115: 3318, 2005; Lancet 377: 1276, 2011; molecules and cells J. Clin. Endo. Metab. 96: 600, 2011; J. Clin. Path. 64: 1042, 2011)

Pathology of Osteoporosis
WebPath Tutorial

Heavy calcium intake (popular with the Tums manufacturers, of course) remains "unproven" as a means of preventing the dread late effects of osteoporosis. Children and teens are exhorted to take lots of calcium to prevent osteoporosis in old age. Not only are good current epidemiologic studies not there (meta-analysis BMJ 333: 775, 2006), the idea also doesn't make sense -- osteoporosis reflects a lack of matrix protein, not a lack of calcium. Your lecturer believes that old work on plentiful calcium preventing "bone loss" on x-ray resulted from its preventing osteomalacia (which of course it often does), not osteoporosis. The two look the same on imaging studies. Go figure.

However, the idea that taking extra calcium even when you're a kid is important because it keeps you from getting osteoporosis years later is still dogma (despite the meta-analysis Br. Med. J. 333: 775, 2006, which reached the same conclusion based on clinical studies as I did by reasoning from the basic pathology). This government health scare remains politically correct, and disclaimers are required. ("Recent research has raised doubts about the efficacy of calcium supplementation in preventing fractures; however, adequate calcium intake remains important." -- Am. J. Clin. Nutr. 85: 1361, 2007). Tell your patients "Uncle Sam still stays you need a lot of calcium", just to cover yourself when they break a bone.

* Paradoxically, the amino-terminal end of parathyroid hormone increases the formation and total mass of bone, and this is now finding clinical use: NEJM 344: 434, 2001.

{46507} osteoporosis, gross
{13844} osteoporosis, histology (thin trabeculae)

Osteoporosis
Tom Demark's Site

Osteoporosis
WebPath Tutorial -- comments are down right now

Osteoporotic compression fracture
WebPath Tutorial -- comments are down right now

OSTEOMALACIA

OSTEITIS FIBROSA CYSTICA and RENAL OSTEODYSTROPHY

{46509} osteomalacia, thick unmineralized osteoid seams
{46510} osteomalacia, von Kossa stain for calcium (calcified is black, non-calcified is orange)
{12027} renal rickets
{12734} osteitis fibrosa cystica (osteoclast city!)

* FLUOROSIS

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS is a common, usually asymptomatic process, in which ligaments and tendons ossify, especially around the lower vertebral bodies, linking them. They look like the drippings of wax candles.

PAGET'S OSTEITIS DEFORMANS (Am. Fam. Phys. 65: 2069, 2002; J. Clin. Inv. 115: 200, 2005; Lancet 372: 155, 2008; NEJM 368: 644, 2013)

{13384} Paget's disease, skull, gross
{18781} Paget's disease, skull
{09376} Paget's disease, bowed lower extremities
{09377} Paget's disease, bowed upper extremities
{38210} Paget's disease, histology
{18810} Paget's disease, histology
{13847} Paget's disease, histology
{13850} Paget's disease, polarized light; woven bone

Paget's osteitis deformans
WebPath Tutorial -- comments are down right now

Paget's osteitis deformans
WebPath Tutorial -- comments are down right now

Paget's osteitis deformans
Tom Demark's Site

Paget's Osteitis Deformans
Tom Demark's Site

Paget's osteitis deformans
Tom Demark's Site

HYPERTROPHIC OSTEOARTHROPATHY

OSTEONECROSIS OF THE JAW (Clin. Tox. 45: 753, 2007; Am. J. Med. 121: 475.e3, 2008; South. Med. J. 101: 160, 2008; Ortho. Clin. N.A. 40: 223, 2009):

* Bones are a perennial symbol of human mortality, and in a larger sense, of all of human biology. "A soft tongue can break hard bones": Proverbs 28:19. "Bone of my bone..." -- Adam. "Cursed be he who moves my bones" -- Shakespeare's epitaph. "Them bones, them bones gonna rise..." -- Afro-American Spiritual. As a kid, I was haunted by Yeats's cryptic ghost tale The Dreaming of the Bones. As an Irishman, Yeats couldn't actually say, "Isn't it time we forgave the English?", but the very-short piece is recommended reading in any era of political hatred.

INTRODUCTION TO BONE AND SOFT TISSUE TUMORS

Sarcoma Images
University of Washington
Pictures and comments

Bone Tumors
NJ Med Path Dept
Nice tutorial

Bone Tumors
Henry DeGroot's site
X-rays and pathology

* OSTEOPOIKILOSIS is a non-disease in which there are patches of extra-dense bone around the skeleton. It fools the inexperienced into thinking there are osteoblastic metastases.

FIBROUS DYSPLASIA (Arch. Path. Lab. Med. 137: 134, 2013)

Fibrous dysplasia
Bryan Lee

Fibrous dysplasia
Woven bone
Tom Demark's Site

Fibrous dysplasia
NJ Med Pathology
Case study

Aneurysmal bone cyst
WebPath Tutorial -- comments are down right now

Aneurysmal bone cyst
WebPath Tutorial -- comments are down right now

Aneurysmal bone cyst
WebPath Tutorial -- comments are down right now

Aneurysmal bone cyst
NJ Med Pathology
Case study

BONE-FORMING TUMORS

{10830} osteoid osteoma, histology

Osteoid osteoma
WebPath Tutorial -- comments are down right now

Osteoid osteoma
WebPath Tutorial -- comments are down right now

Adamantinoma
NJ Med Pathology
Case study

Osteoid osteoma
NJ Med Pathology
Case study

{05755} osteosarcoma, x-ray
{05906} osteosarcoma, gross
{05909} osteosarcoma, gross
{05927} osteosarcoma, gross
{05930} osteosarcoma, gross
{24747} osteosarcoma, gross
{21118} osteosarcoma, with pathologic fracture
{10322} parosteal osteosarcoma, gross
{05838} parosteal osteosarcoma, x-ray
{05864} osteosarcoma, histology
{25613} osteosarcoma, histology
{32123} osteosarcoma, histology

Osteosarcoma
Great labels
Romanian Pathology Atlas

Osteosarcoma
Pittsburgh Pathology Cases

Osteosarcoma
Pittsburgh Pathology Cases

Osteosarcoma
Tom Demark's Site

Osteosarcoma
Tom Demark's Site

Osteosarcoma
Tom Demark's Site

High-grade osteosarcoma
NJ Med Pathology
Case study

Osteosarcoma
Osteoid production
WebPath Photo

Parosteal osteosarcoma
WebPath Tutorial -- comments are down right now

Clickable osteosarcoma
WebPath Tutorial -- comments are down right now

Osteosarcoma
WebPath Tutorial -- comments are down right now

Osteosarcoma
WebPath Tutorial -- comments are down right now

Osteosarcoma
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

CHONDROMATOUS TUMORS (remember cartilage often undergoes dystrophic calcification)

Cartilage Exhibit
Virtual Pathology Museum
University of Connecticut

{05842} exostosis ("osteochondroma")

Osteochondroma
WebPath Tutorial -- comments are down right now

Osteochondroma
WebPath Tutorial -- comments are down right now

Osteochondroma
WebPath Tutorial -- comments are down right now

Osteochondroma
WebPath Tutorial -- comments are down right now

Osteochondroma
NJ Med Pathology
Case study

Chondroma
Great labels
Romanian Pathology Atlas

Enchondroma
NJ Med Pathology
Case study

Enchondromatosis, 1870's
Not Olliers, but a hands-and-feet variant
College of Physicians of Philadelphia

Myxoid Chondrosarcoma
Electron micrographs
VCU Pathology

Chicken-wire chondroblastoma
NJ Med Pathology
Case study

Low-grade chondrosarcoma
Soap bubble x-ray
NJ Med Pathology -- Case study

High-grade chondrosarcoma
NJ Med Pathology
Case study

{05958} chondrosarcoma, gross
{09637} chondrosarcoma, gross
{46512} chondrosarcoma, gross
{49494} chondrosarcoma, gross
{09643} chondrosarcoma, lost its differentiation
{09649} chondrosarcoma, rib, gross
{10319} chondrosarcoma, pubis
{08997} chondrosarcoma, histology
{35999} chondrosarcoma, histology
{08998} chondrosarcoma, histology

Chondrosarcoma
Pittsburgh Pathology Cases
Great x-ray

Chondrosarcoma
WebPath Tutorial -- comments are down right now

Click on the chondrosarcoma
WebPath Tutorial -- comments are down right now

Chondrosarcoma
WebPath Tutorial -- comments are down right now

Click on the chondrosarcoma
CT scan
WebPath Tutorial -- comments are down right now

Chondrosarcoma
WebPath Tutorial -- comments are down right now

TUMORS OF UNCERTAIN ORIGIN

{49496} Ewing's sarcoma, resection specimen
{46408} Ewing's sarcoma, gross
{08470} Ewing's sarcoma, gross
{05812} Ewing's sarcoma
{38204} Ewing's sarcoma, histology
{40496} Ewing's sarcoma, histology (reticulin stain)
{46410} Ewing's sarcoma, small undifferentiated cells
{46411} Ewing's sarcoma, widespread necrosis

Ewing's Sarcoma
Pittsburgh Illustrated Case

Ewing's sarcoma
WebPath Tutorial -- comments are down right now

Ewing's sarcoma
WebPath Tutorial -- comments are down right now

Ewing Sarcoma
H&E
Wikimedia Commons

Ewing's Sarcoma
NJ Med Pathology
Case study

Giant cell tumor
WebPath Tutorial -- comments are down right now

Giant cell tumor
x-rays
WebPath Tutorial -- comments are down right now

Giant cell tumor
WebPath Tutorial -- comments are down right now

Giant Cell Tumor of Bone
NJ Med Pathology
Case study

{21123} malignant fibrous histiocytoma, trust me
{21127} malignant fibrous histiocytoma, trust me

Paget's disease
Malignant fibrous histiocytoma
NJ Med Pathology case study

Chordoma
NJ Med Pathology
Case study

Joint myxoma
Pittsburgh Pathology Cases

METASTASES TO BONE

Metastases
WebPath Tutorial -- comments are down right now

Metastases
WebPath Tutorial -- comments are down right now

Osteoblastic metastases
x-ray
WebPath Tutorial -- comments are down right now

Osteoblastic metastases
x-ray
WebPath Tutorial -- comments are down right now

Osteolytic metastases
x-ray
WebPath Tutorial -- comments are down right now

Osteolytic metastases
x-ray
WebPath Tutorial -- comments are down right now

Bone metastases
WebPath Tutorial -- comments are down right now

Bone metastases
WebPath Tutorial -- comments are down right now

REMEMBER: Plasma cell myeloma, malignant lymphoma (Arch. Path. Lab. Med. 133: 1868, 2009), and eosinophilic granuloma (a low-grade tumor of dendritic macrophages) are other important causes of "bone tumors".

Eosinophilic granuloma
NJ Med Pathology
Case study

SOFT TISSUE TUMORS AND QUASI-TUMORS

Soft Tissue Pathology
Sampurna Roy, MD
Lots of photos and good text

Lipomatous and Myxoid Tumors
Histopathology and essay
For pathologists

Soft tissue
"Pathology Outlines"
Nat Pernick MD

{21146} malignant fibrous histiocytoma, gross (trust me on this and the following MFH's)
{09019} malignant fibrous histiocytoma, histology
{09020} malignant fibrous histiocytoma, histology
{09021} malignant fibrous histiocytoma, histology
{09119} malignant fibrous histiocytoma, electron micrograph; see the macrophage features?

Malignant fibrous histiocytoma
Tom Demark's Site

{05810} lipoma, gross
{12172} lipoma, gross
{12171} lipoma, gross
{15460} lipoma, colon
{40056} lipoma, gross

Lipoma

KU Collection

Lipoma
Variant with some fibrosis
KU Collection

Lipomas
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

{46354} hibernoma, histology

Brown fat
Rrelatively large vacuoles
ERF/KCUMB

Hibernoma
Tom Demark's Site

{25412} adrenal myelolipoma
{25413} adrenal myelolipoma

{05804} liposarcoma, gross
{05807} liposarcoma, gross (a big one!)
{10607} liposarcoma, gross
{09004} liposarcoma, histology
{24750} liposarcoma, fat stain

Liposarcoma

WebPath Photo

Liposarcoma

WebPath Photo

Liposarcoma

WebPath Photo

BIBLIOGRAPHY / FURTHER READING

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