Recognize normal bone and the non-neoplastic bone and joint diseases on gross, radiographic and microscopic images
Key questions
Q1What does normal adult cancellous bone look like?
Pink, smooth lamellar trabeculae (parallel layers, flat osteocytes in lacunae) with hematopoietic marrow and fat between them; no woven bone.
Q2How do you recognize a growth plate on a slide?
Hyaline cartilage (pale purple) on one side, columns of chondrocytes, then calcified cartilage cores covered by pink bone (primary spongiosa) on the other.
Q3How does chronic osteomyelitis look?
Marrow replaced by fibrous tissue with lymphocytes and plasma cells beside dead or remodeled bone; in the gross/X-ray, sequestrum wrapped by involucrum.
Q4How does fracture callus look?
A mix of cartilage and haphazard woven bone (irregular, plump, crowded osteocytes, no lamellae) — normal repair, but woven bone in an adult otherwise means disease.
Q5How does osteoporosis look grossly?
Vertebral bodies with thin, sparse trabeculae; a vertebra may be collapsed (compression fracture) so the discs above and below nearly touch.
Q6What is the classic Paget image?
Mosaic (jigsaw) pattern of lamellar bone — irregular blue cement lines between bone fragments — with fibrovascular marrow and big osteoclasts.
Q7How do RA and gout appear in the lab?
RA: hands with MCP swelling and ulnar deviation of the fingers; rheumatoid nodule = central fibrinoid necrosis ringed by palisading macrophages. Gout: tophus = pale amorphous/feathery crystal deposits ringed by macrophages and foreign-body giant cells.
Normal = lamellar trabeculae + marrow. Look for woven bone (callus, Paget), fibrosed marrow + chronic inflammation (chronic osteomyelitis), thin trabeculae / collapsed vertebra (osteoporosis), mosaic cement lines (Paget — a favorite), fibrinoid necrosis with palisading (rheumatoid nodule), crystals ringed by giant cells (tophus).
Name that image — try before you reveal
Normal: what zone of bone is this?Reveal
Growth plate / endochondral ossification — pale hyaline cartilage on the left becomes calcified cartilage covered by pink bone trabeculae on the right.
Normal (polarized light): what kind of bone?Reveal
Lamellar trabecular bone with hematopoietic marrow — polarized light shows the parallel lamellae; trabeculae give strength without the weight of solid bone.
Bone with fibrosed marrow and a cluster of inflammatory cells.Reveal
Chronic osteomyelitis — marrow fibrosis and lymphoplasmacytic inflammation next to damaged bone.
Upper humerus X-ray: what kind of fracture, and why?Reveal
Pathologic fracture (through a primary sarcoma) — a break through diseased bone — tumor, metastasis, metabolic bone disease — rather than normal bone.
Mid-humerus after a car crash: what type of fracture?Reveal
Compound (open) fracture — bone breaks through the skin → risk of mixed-organism osteomyelitis.
New bone lined by a row of cells near an old fracture.Reveal
Healing fracture (callus, woven bone) — osteoblastic rimming — a line of osteoblasts building new woven bone, later remodeled to lamellar bone.
Sectioned vertebral column: what is wrong with the bodies?Reveal
Osteoporosis — thin, sparse trabeculae in porous vertebral bodies.
The middle vertebra has vanished between two discs.Reveal
Osteoporotic compression fracture — collapse of a weakened vertebral body.
Irregular trabeculae with many cement lines and fibrovascular marrow.Reveal
Paget disease (mixed phase) — active osteoclasts and osteoblasts laying down disorganized bone.
Polarized light: bone crossed by a jigsaw of lines.Reveal
Paget disease — mosaic pattern — irregular cement lines between bone units; the classic Paget image.
Two femoral heads: which is abnormal?Reveal
Left normal; right osteoarthritis — normal = smooth, glistening articular cartilage; OA = rough, dense, irregular (eburnated) surface. Osteonecrosis can predispose to OA.
What joint disease do these hands show?Reveal
Rheumatoid arthritis — swollen MCPs with ulnar deviation of the fingers and radial deviation of the wrist.
Subcutaneous nodule: pale center with a rim of cells.Reveal
Rheumatoid nodule — central fibrinoid necrosis surrounded by palisading macrophages, then lymphocytes.
Pale amorphous deposit ringed by large cells.Reveal
Tophaceous gout (tophus) — urate crystal aggregates (dissolved in processing) surrounded by macrophages and foreign-body giant cells.
Memory hook
In the lab, always ask: lamellar or woven? Woven bone in an adult = callus, Paget or tumor.
HY · Step 1
Paget mosaic bone and empty lacunae of osteonecrosis are the two most tested bone histology images.
LO 2
Recognize the benign and malignant bone neoplasms on gross, radiographic and microscopic images
Key questions
Q8How does an osteochondroma look?
X-ray/gross: a bony stalk growing away from the joint, continuous with the cortex and marrow, capped by cartilage. Micro: hyaline cartilage cap (purple) transitioning to cancellous bone (pink) by endochondral ossification.
Q9How does an aneurysmal bone cyst look?
Gross: multiloculated, spongy mass of blood-filled cysts. Micro: cyst walls of fibroblasts, osteoclast-like giant cells, reactive woven bone and red cells. Benign, usually metaphyseal.
Q10How does osteosarcoma look?
Gross: large gray-white, hemorrhagic mass in the metaphysis destroying cortex and lifting periosteum. Micro: pleomorphic malignant cells directly making lace-like osteoid/woven bone.
Q11How does chondrosarcoma look?
Gross: lobulated, glistening gray-blue, bubbly cartilage mass, often hemorrhagic, in pelvis/shoulder. Micro: crowded atypical chondrocytes in lacunae within blue hyaline matrix, invading bone.
Q12How does Ewing sarcoma look?
Gross: gray-white tumor in the diaphysis, spreading in the medulla and cortex. Micro: monotonous sheets of small round blue cells with scant cytoplasm.
Q13What features separate benign from malignant bone tumors on images?
Benign: well-circumscribed, narrow zone of transition, bland cells, maturation (osteochondroma cap → bone). Malignant: destruction of cortex, soft tissue extension, pleomorphism, mitoses, necrosis, tumor cells making matrix directly.
Benign: osteochondroma (cartilage cap on a stalk — purple then pink), aneurysmal bone cyst (blood-filled spongy cysts, giant cells). Malignant: osteosarcoma (destructive metaphyseal mass, malignant cells making osteoid), chondrosarcoma (bubbly lobulated cartilage, atypical chondrocytes), Ewing (diaphysis, small round blue cells).
Name that image
X-ray and specimen from a teenager's knee lump.Reveal
Osteochondroma — bony stalk projecting from the metaphysis away from the joint, with a cartilage cap.
Purple on the left, pink on the right.Reveal
Osteochondroma (histology) — hyaline cartilage cap undergoing endochondral ossification into bone.
Spongy, multiloculated bone lesion.Reveal
Aneurysmal bone cyst — blood-filled cysts separated by thin septa; benign, metaphyseal.
Multinucleated giant cells, plump spindle cells and red cells.Reveal
Giant cell–rich lesion (aneurysmal bone cyst wall / giant cell tumor) — osteoclast-like giant cells; location decides: epiphysis in an adult = GCT, blood-filled cysts = ABC.
Femur with a large mass bulging from the metaphysis.Reveal
Osteosarcoma — destructive mass breaking through cortex and lifting periosteum.
Atypical cells between pink, irregular matrix.Reveal
Chondrosarcoma — lobulated cartilage tumor of the central skeleton in an older adult.
Pale, vesicular chondrocytes invading bone.Reveal
Chondrosarcoma (histology) — atypical chondrocytes in lacunae; grade by cellularity and atypia.
Tumor in the shaft of a long bone.Reveal
Ewing sarcoma — diaphyseal medullary tumor extending into the cortex.
Sheets of identical round blue cells.Reveal
Ewing sarcoma (histology) — small round blue cell tumor; confirm CD99 and t(11;22).
HY · Step 1
Small round blue cell tumors of childhood: Ewing, rhabdomyosarcoma, neuroblastoma, lymphoma, Wilms, retinoblastoma — separate them with IHC and translocations.
LO 3
Recognize the soft tissue lesions on gross and microscopic images
Key questions
Q14How does fibromatosis look?
Long, sweeping bundles of bland fibroblasts with collagen and slit-like vessels that infiltrate between skeletal muscle fibers (the muscle is trapped at the edge).
Q15How does a plexiform neurofibroma look grossly?
A tangle of thickened nerve fascicles — "bag of worms" — essentially diagnostic of NF1.
Q16How does liposarcoma look?
Gross: a large, yellow, fatty, lobulated mass (often deep thigh or retroperitoneum). Micro: fat cells of varying size with fibrous septa, atypical hyperchromatic stromal cells and lipoblasts.
Q17What does lymphedema-associated angiosarcoma look like clinically?
A chronically swollen limb with thickened, discolored skin and red-brown to purple nodules that ulcerate and bleed.
Q18What is an intramuscular myxoma?
A benign tumor within skeletal muscle: gross = white, glistening, gelatinous nodules in muscle; micro = very few bland spindle/stellate cells in abundant pale myxoid matrix with scant vessels. (Its bland, hypovascular look separates it from myxoid liposarcoma, which has lipoblasts and chicken-wire capillaries.)
Fibromatosis: bland fibroblast bundles infiltrating muscle. Plexiform neurofibroma: "bag of worms" (NF1). Liposarcoma: huge yellow fatty mass with atypical cells/lipoblasts. Angiosarcoma: nodules on a lymphedematous limb. Myxoma: gelatinous white nodules in muscle, bland cells in myxoid matrix.
Name that image
Bland fibroblasts streaming into skeletal muscle around a stretched vessel.Reveal
Fibromatosis (desmoid) — long sweeping fascicles of bland spindle cells; shoulder, chest wall, neck, thigh, or postpartum abdominal wall; recurs, does not metastasize.
A tangle of thickened, rope-like nerves.Reveal
Plexiform neurofibroma — "bag of worms"; the hallmark tumor of NF1 (not Gardner syndrome) and the precursor of MPNST.
A large yellow, lobulated fatty mass from deep tissue.Reveal
Liposarcoma (well-differentiated) — deep or retroperitoneal fat = liposarcoma until proven otherwise.
Fat cells of varying size with fibrous stroma and atypical cells.Reveal
Lymphedema-associated angiosarcoma — malignant endothelial tumor in long-standing lymphedema (e.g., after axillary dissection).
Two white gelatinous nodules within muscle.Reveal
Intramuscular myxoma — benign, glistening, gelatinous tumor of unknown histogenesis; does not recur after complete excision.
Muscle on the left, pale bland matrix on the right.Reveal
Myxoma (histology) — few bland cells in abundant myxoid matrix, scant vessels.
Lab DDx: pale myxoid tumors
Lesion
Cells
Vessels
Clue
Intramuscular myxoma
Very few, bland
Scant
Benign, inside muscle
Myxoid liposarcoma
Bland + lipoblasts
Chicken-wire capillaries
Thigh, 30–40s, t(12;16)
Schwannoma (Antoni B)
Loose Schwann cells + Antoni A areas
Hyalinized
Encapsulated, on a nerve
Nodular fasciitis
Plump fibroblasts, tissue-culture look
Extravasated RBCs
Forearm, weeks
Application questions
1. A lab slide shows bone composed of irregular fragments separated by a jigsaw of cement lines, with fibrovascular marrow. The patient's most likely lab abnormality is:
Hypercalcemia
Isolated elevated alkaline phosphatase
Hypophosphatemia
Elevated PTH
Monoclonal spike
Answer
B. Mosaic bone = Paget disease; labs show isolated ↑ ALP with normal calcium and phosphate.
2. A slide shows marrow replaced by fibrous tissue with lymphocytes and plasma cells next to dead bone. The patient had an open fracture a year ago and now has a draining sinus. Diagnosis?
Acute osteomyelitis
Chronic osteomyelitis
Osteoid osteoma
Paget disease
Fracture callus
Answer
B. Chronic osteomyelitis: fibrosis and chronic inflammation, sequestrum and involucrum, draining sinus.
3. A specimen from a 15-year-old shows a bony stalk with a cartilage cap; microscopy shows purple hyaline cartilage merging into pink cancellous bone. Which statement is true?
It arises in the diaphysis
Its marrow is continuous with the parent bone
It is usually malignant
It is caused by t(11;22)
It needs chemotherapy
Answer
B. Osteochondroma: cortex and marrow are continuous with the parent bone; benign; EXT genes.
4. A resected tumor from the femoral shaft of a 10-year-old shows sheets of identical small round blue cells. Which test best confirms the diagnosis?
Keratin stain
CD99 and EWSR1 rearrangement
S-100
Desmin only
Congo red
Answer
B. Ewing sarcoma: CD99 (MIC2) and EWSR1-FLI1 t(11;22).
5. A gross specimen shows a tangle of markedly thickened nerve fascicles from the neck of a 12-year-old with many café-au-lait spots. What is the major long-term risk?
Bilateral acoustic schwannomas
Malignant peripheral nerve sheath tumor
Meningioma
Osteosarcoma
Colon cancer
Answer
B. Plexiform neurofibroma (NF1) carries a lifetime MPNST risk (~10%).
6. A slide shows bland fibroblasts in long sweeping bundles with collagen infiltrating between skeletal muscle fibers. What is the expected behavior?
Regresses spontaneously within weeks
Recurs locally but does not metastasize
Metastasizes to lymph nodes
Metastasizes to lung early
Transforms to liposarcoma
Answer
B. Fibromatosis (desmoid): infiltrative, recurrent, non-metastasizing.
Each objective opens with the one-line answer. Yellow boxes are high-yield Step 1 add-ons and may go beyond the lecture.