BONE PATHOLOGY

BONE

NORMAL

Normal constituents of bone

• § -organic + inorganic matrix (calcium hydroxyapatite)
• § -proteins: collagen I, cell-adhesion proteins, Ca-binding proteins
• § -activity of cells regulated by growth factors:
• § (FGF, PDGF, IGF, TGF-B)

What are the cell types in bone?

• § -osteoprogenitor cells
• § -osteoclast (derived from monocytes, multinucleated cell that eats bone)
• § -osteocyte (housed in lacunae)
• § -osteoblast (derived from osteoprogenitor cells, rim trabeculae and mineralize bone)

PAGET DISEASE

• § Clin: older adults>40
• § Etiology: slow virus infection of paramyxovirus of osteoclasts, (virus particles identified in nuclei and cytoplams of osteoclasts)

Pathophysiology:

1. osteolytic phase:

• § LARGE osteoclasts w/ ↑ number of nuclei
• § resorption pits

2. mixed phase:

• § -“mix” of osteoclasts and osteoblasts
• § -fibrous tissue in marrow
• § -new bone woven or lamellar
• § 3. osteosclerotic phase: burnt out phase.
• § thickened trabeculae
• § cortex is porous (poor structural stability)
• § -“mosaic pattern of cement lines”

Summary:

• § Disruption of balance b/w mineralization and resorption. Net is effect is a gain in bone mass.

Radiologic features:

• § early-radiolucency
• § late-increased bone density, microfractures

AVASCULAR NECROSIS (OSTEONECROSIS)

What are the causes of AVN?

• § Fracture
• § Corticosteroids
• § Alcohol
• § Sickle cell anemia

Blood vessel-related:

• § 3. Thrombosis/Embolism
• § 4. Vasculitis
• § 5. Venous HTN

 

Pathologic features:

• § Cartilage→ preserved from synovial fluid nourishment

Subchondral bone

• § -infarct (wedge-shaped)
• § -necrosis (bone and marrow), collapse of trabeculae, dead bone w/ empty lacunae, ruptured adipocytes results in insoluble Ca soaps
• § fibrosis of marrow
• § -“creeping substitution” (osteoclasts partially remove necrotic trabeculae, remainder of dead trabeculae act as scaffolding)

DEVELOPMENTAL ABNORMALITIES

ACHONDROPLASIA

• § Clin: AD inheritance, shortened proximal extremities, normal trunk, enlarged head w/ bulging forehead

Micro:

• § irregular growth plates:
• § clusters of chondrocytes
• § 2. horizontal struts of bone which seal growth plate prematurely

OSTEOGENESIS IMPERFECTA

Deficiency in which type of collagen?

• § -Type I collagen

Where are mutations located?

• § -alpha1 and 2 chains of collagen

How many types of OI?

• § Four different subtypes

Name 4 clinical features:

• § OI Type Ià post-natal fractures, blue sclerae, hearing impairment, joint laxity

 

OSTEOPOROSIS

Definition

• § -increased porosity of bone resulting from a reduction in bone mass

Primary vs. secondary osteoporosis?

Primary:

• § -post-menopausal , senile, idiopathic

Secondary:

• § -↑PTH: SCC lung, hyperparathryroidism, CRF
• § hypo/hyperthyroidism
• § myeloma

Contributing factors to osteoporosis:

• § ↑age
• § ↓physical activity
• § ↓ Ca
• § ↓estrogen (post-menopause)
• § Gross: loss of cancellous bone, accentuation of vertical trabeculae in spine

Micro:

• § thin trabeculae
• § -↑in osteoclastic activity
• § -↑ resorptive pitting
• § Diagnosis: bone densitometry, iliac crest biopsy
• § Xray: flattening of vertebral bodies

 

OSTEOPETROSIS

• § -secondary to deficient osteoclast activity

Gross features:

• § -long bones bulbous (Erlenmyer flask deformity)
• § -compression of neural foramina
• § -medullary cavity: primary spongiosa fills medullary cavity → matures only to woven bone
• § Prog and symptoms: cranial nerve impairment, extramedullary hematopoeisis resulting in hepatosplenomegaly

 

RICKETS AND OSTEOMALACIA

• § -deficiency in vitamin D resulting in hypocalcemia
• § -accumulation of unmineralized bone matrix
• § Clin: bone pain and weakness (from hypoCa)
• § -children:
• § -cup-shaped growth plates (knee and wrist)
• § -“curves”: bowing of legs, lumbar lordosis, pigeon chest
• § -Adults, undermineralized bone→ causes osteopenia and fractures
• § Micro:
• § children
• § growth plate: thickened, poorly defined
• § tongues of uncalcified cartilage into metaphysis
• § adults
• § osteoid matrix + disorganized trabeculae
• § irregular junction between osteoid and bone
• § Xray: generalized osteopenia with multiple #
• § Dx: biopsy of long bone or iliac crest

RICKETS:

OSTEOMALACIA

HYPERPARATHYROIDISM

What are the functions of PTH/vit D?

Bones:

• § ↑Ca resorption from bones by activation of osteoclasts (vit D helps here)

Gut:

• § 2. ↑Ca absorption in gut (vit D helps here)

Kidneys:

• § 3. ↑conversion of vit D to active dihydroxy form
• § 4. ↑urinary excretion of PO4 (to lower serum PO4)
• § 5. ↑Ca resorption in renal tubules (vit D helps here)

Mechanisms of hypercalcemia

• § osteolytic metastases
• § release of PTH-related protein

 

What are the effects of hyperparathryoidism on different organs in the body?

• § BONE:
• § Osteoporosis-like changesà mostly in cortical bone
• § 2.  Dissecting osteitisà osteoclasts bore through centre of trabeculae
• § 3.  Brown tumour of hyperparathyroidism
• § 4.  Osteitis fibrosa cysticaà fibrosis + hemorrhage + cysts + peritrabecular fibrosis?

URINARY TRACT

• § -nephrolithiasis

Metastatic calcification

• § -lungs, heart, vessels, stomach

Secondary hyperparathryoidism

• § usually secondary to chronic renal insufficiency
  • Ø results in ↓ PO4 excretion
  • Ø (↑serum PO4 suppresses Ca++ levels)
  • Ø ↓ Ca++ levels stimulates PTH secretion

 

Pathologic features in the bone:

• § Cortical bone affected most.
• § 1Dissecting osteitis
• § →osteoclasts bore through centre of trabeculae
• § 2Brown tumour of hyperparathyroidism
• § →see below
• § 3Generalized osteitis fibrosa cystica
• § →peritrabecular fibrosis + cystic brown tumours

 

What is renal osteodystrophy?

• § -skeletal conditions seen in the setting of CRF
• § ↑ osteoclast resorption mimicking osteitis fibrosa cystica
• § delayed matrix mineralization
• § osteosclerosis
• § growth retardation
• § osteoporosis

 

OSTEOMYELITIS

Pyogenic Osteomyelitis

• § Routes of entry:
• § Hematogenous: more in kids
• § Direct extension

 

• § Organisms involved:
• § “SEPK”
• § S.aureus and strep pyogenes
• § E. coli
• § Pseudomonas
• § Klebsiella

Hemophilus influenzae

 

• § Pathophysiology:
• § -Bacteria spread along haversian system or medullary cavityà subperiosteal abscesses impair blood supplyà draining sinuses

Gross:

• § infants: joint and epiphysis
• § children: metaphysis
• § →subperiosteal abscess (can lift bone up and kill it)
• § →(dead bone = sequestrum)
• § →new bone (involucrum) can be deposited around dead bone
• § adults: joint infection and extensive bone damage
• § Micro: nφ,lφ,pφ, new bone formation, bv and fibrosis
• § TB à spine most common
• § syphilisà pφ and necrotic bone

JOINTS

OSTEOARTHRITIS

• § Clin: >50yr., symmetrical joints (knee, hip, DIP, PIP)

Path:

Cartilage:

• § fibrillation(vertical or horizontal splitting),
• § cloning of chondrocytes

-articular surface:

• § 3) granular and soft and eventually →
• § 4) eburnation with loss of cartilage
• § -bone:
• § 5) microfractures→ joint mice
• § 6) subchondral cysts filled with mucoid fluid
• § 7) sclerosis of cancellous bone (thickening)
• § osteophytes
• § Synovium: mild chronic inflm.

 

RHEUMATOID ARTHRITIS

Pathogenesis

• § Exposure to arthritogenic microbial Ag (?EBV)
• § Autoimmune reaction with CD4+ T cells, B cells which prod. IgM Ab to Fc portion of IgG Ab
• § Mediators of injury: IL-1, TNFa
• § Genetic susceptibility: HLA-DR4/DR1 allele
• § Clinical presentation (age, gender)
• § Organs affected and assoc pathology:

Joints:

• § -subchondral
• § lymphoid nodules
• § subchondral cysts
• § osteoporosis
• § -synovium:
• § chr. inflm w. plasma cells (perivascular), lymphoid follicles
• § fibrin overlying surface
• § neutrophils overlying surface
• § synovial hyperplasia & hypertrophy
• § vasculitis
• § pannus “hypertrophied synovium with inflm” overlying articular surfaceà eventually becomes fibrotic and bridges joint “fibrous ankylosisà bony ankylosis

Skin:

• § -rheumatoid nodules (elbows, forearm, lumbosacral area)
• § -palisading granuloma (central zone of fibrinoid necrosis surrounded by lφ,pφ,hφ)

Blood vessels

• § -vasculitis of small to medium size arteries

Name 5 seronegative arthropathies

“Apple PIE And Raisons”

• § Arthritis:

• § Psoriatic arthritis
• § Infectious arthritis
• § Enteropathic arthritis

 

• § Ankylosing spondylitis

 

• § Reiter syndrome

CRYSTAL ARTHROPATHIES

GOUT

“old fat people who pee(thiazides) on lead”

• § RF: age, genetic predisposition, alcohol, obesity, drugs (thiazides), lead toxicity, hyperuricemia (diet, genetic, tumor lysis).

Deposition of what type of crystals?

• § -monosodium urate crystals
• § -needle shaped negatively birefringent (on 1^st order compensation)

Path: (what are the features at each stage?)

1. 1. Acute arthritis

• § -synovium: dense nφ + chr. infm
• § -synovial fluid: crystals

1. 2. Chronic tophaceous arthritis

• § -synovium: hyperplastic + hypertrophy + pannus

¨   = joint destruction

1. 3. Tophi

• § -Gross: chalky white
• § -large amorphous aggregates of urate crystals surrounded by histiocytes, lymphocytes and GCs

1. 4. Gouty nephropathy

• § -crystal in medulla→tophi, free uric acid crystals, uric acid stones,
• § Location of attacks
• § -1^st MTP, insteps, ankles, heels,
• § Associated with HTN

 

PSEUDOGOUT (CALCIUM PYROPHOSPHATE)

• § Clin: →50yrs, assoc/ hypothyroid, hypomagnesemia, hyperPTH, hypoT4, hemochromatosis, DM, joint damage

Location of crystal deposition

• § -menisci, intervertebral discs
• § -may seed joint and elicit nφ

Deposition of what type of crystals?

-rhomboid crystals, weakly positive birefringent + histiocytes/GCs

SYNOVIAL CHONDROMATOSIS

• § Clin: presents with joint locking, pain, swelling micro: mass of cloned, crowded, atypical chondrocytes surrounded by synovium

PIGMENTED VILLONODULAR SYNOVITIS CLIN: YOUNG ADULTS, SYNOVIAL LINING OF JOINTS (USU KNEE WITH EFFUSION AND MILD PAIN)

• § Treatment: excision, but may recur locally
• § Gross: brown-yellow with firm nodular feel
• § Micro:
• § -hyperplastic and papillary synovium
• § -mononuclear cells and multinuclear giant cells with hemosiderin deposition
• § -minimal infm, NO mitoses
• § IHC: CD68 (stromal and giant cells)

• § Clin: jaws in adults
• § Gross: solid and cystic types
• § Micro: “looks like a developing tooth” biphasic pattern: outer tall columnar layer and inner stellate reticulum layer +/- squamous metaplasia (acanthomatous type)
• § Clin: adolescents, <1.5cm, pain at night relieved by asa b/c caused by e2 prostaglandin secretion, cortex
• § Gross: central nidus (which is the tumor) is soft, periphery is sclerotic bone
• § Micro:
• § 1centre: anastomosing trabeculae of woven bone, not rimmed by osteoblasts, vascular connective tissue
• § 2surrounded by a variably reactive thick layer of dense bone
• § Addt’l w/u: can xray specimen to identify nidus
• § Clin: adolescents, male, spine, >1.5cm
• § Gross: no central nidus.
• § Micro: looks like osteoid osteoma with a bit more vascularity
• § Clin: slow growing, benign overgrowth over cortex of flat (skull, mandible) bone. Solitary.
• § -Multiple if assoc/ Gardner’s
• § Micro: dense lamellar bone rimmed by osteoblasts, surrounded by vascular, loose connective tissue

OSTEOGENIC TUMOURS

AMELOBLASTOMA (ADAMANTINOMA OF JAW)

OSTEOID OSTEOMA

OSTEOBLASTOMA

OSTEOMA

 

MALIGNANT TUMORS

• § most common: myeloma, osteosarcoma, chondrosarcoma
• § Clin: young male adults>female; Mets to lungs via bloodstream
• § XRY: Codman triangle.
• § Location: Distal femur, proximal tibia.
• § RF: Paget’s disease, instrumentation, post-radiation OS
• § Good prognosis factors: jaw or distal extremities; low grade, necrosis >90% after preoperative chemotherapy
• § Tx: Limb salvage surgery with chemotherapy
• § Gross: large, gritty, hemorrhage and cyst formationà local invasion into soft tissue and into joint space and surrounding tissues

OSTEOSARCOMA

Variants:

• § conventionalà HG with osteoid
• § (osteoblastic, chondroblastic, fibroblastic {little osteoid})
• § telangiectacticà lytic lesion filled with blood, septae with malignant cells; ddx:ABC;
• § small cellà ddx ES/PNET
• § giant cell
• § low grade centralà firm and fibrous, not fish flesh. Dddx: fibrous dysplasia
• § high grade surfaceà fish flesh
• § periostealà intermediate grade, chondroid lobules with peripheral spindling
• § parostealà low grade, females, can’t flex knee in distal femur, hypocellular spindle cells
• § ***Central usually high grade, surface usually low grade except for 2 exceptions.
• § ***Drug resistance mediated by mdr1

 

ADAMANTINOMA

Clin: young adults, tibia “spindle cell lesion in tibia is practically diagnostic”, cortex and medulla involved

• § Gross: areas of sclerosis and lucency
• § Micro: epithelial islands with perpheral palisading
• § in a dense spindle stroma (may not see epithelial)
• § Prog: good.
• § DDx: metastatic carcinoma

 

GIANT CELL TUMOURS OF BONE

• § Differential diagnosis of giant cell lesions in the bone
• § 1.  Giant cell tumour of bone
• § 2.  Malignant giant cell tumour of bone
• § 3.  Brown tumour of hyperparathyroidism
• § 4.  Giant cell reparative granuloma
• § 5.  Eosinophilic granuloma (hcs dz)
• § 6.  Non-ossifying fibroma
• § 7. Chondroblastoma
• § ABC
• § SBC
• § OS
• § CS
• § Clin: Young women, epiphysis
• § Gross: soft and dark brown is characteristic.
• § Micro: multinucleated and mononuclear cells with similar nuclei. no atypia, mitoses OK.
• § Clin: benign giant cell tumor juxtaposed
• § Micro: looks like MFH, FS or even osteosarc or chondrosarc (no supposed to have matrix)
• § Clin: forms in the setting of secondary hyperparathyroidism
• § parathyroid tumors (adenoma, carcinoma) causing hyperparathyroidism
• § CRF resulting in high levels of PO4 and low levels of Ca++
• § 3-
• § Location: phalanges, spine, clavicle, skull
• § Gross: large lytic, brown (due to hemorrhage)
• § Micro: giant cells with hemorrhage, hemosiderin, microfractures, ingrowth of vascularized fibrous tissue with fibroblastic stromal cells
• § DDx: giant cell tumor (more uniformly distributed giant cells, no interstitial hemorrhage, no fibroblastic stromal cells), giant cell reparative granuloma (clinical correlation as unrelated with hyperPTH)
• § Clin: Giant cell lesion primarily of jaw “repaired b/c punch to jaw”
• § Micro: giant cells and small oval and spindly mononuclear cells, capillaries, hemorrhage, hemosiderin, reactive bone with osteoblastic rimming

GIANT CELL TUMOUR

MALIGNANT GIANT CELL TUMOUR

BROWN TUMOUR OF HYPERPARATHYROIDISM

GIANT CELL REPARATIVE GRANULOMA

 

SMALL CELL TUMOURS OF BONE

MULTIPLE MYELOMA/PLASMACYTOMA

• § Clin: older patients, bone pain & #
• § ▪widespread skeletal lytic lesions
• § ▪hepatosplenomegaly
• § ▪hypercalcemia
• § ▪primary amyloidosis (AL type) and renal insufficiency due to toxicity of light chains Bence Jones proteins
• § Gross: lytic lesions in diaphysis of the skull and long bones
• § Micro: plasma cell infiltrate w/
• § prominent nucleoli, perinuclear hof (Golgi)
• § -Russell bodies (cytoplasmic rods), Dutcher bodies (intranuclear rods), Mott cells

Special studies:

• § serum: monoclonal IgG in serum (monoclonal gamma spike in serum electrophoresis)
• § blood: peripheral smear→rouleaux formation
• § IHC: CD138+, light chain restriction
• § DDx: chronic osteomyelitis (will see other inflm cells + ­ vascularity)
• § “osteosclerotic myeloma”à poeMs: (polyneuropathy, organomegaly, endocrinopathy, monoclonal IgM gammopathy and skin lesions)
• § Clin: boys>5yr., diaphysis of long bones
• § Presentation: pain, fever, weight loss,↑WBC, ↑ESR
• § Gross: soft & fleshy involvement of medulla and cortex
• § Micro: round nuclei with indistinct borders, little cytoplasm, arranged in to irregular lobules by fibrous strands
• § -necrosis, pseudorosette formation
• § IHC: CD99+, EMA-, NSE, syn
• § SS: PAS+
• § Genetics: t(11;22) EWS-FLI1; RT-PCR or FISH
• § Prog: 75% 5yr; poor prog if high grade, viable tumour post chemotx, invasion into soft tissue

EWING SARCOMA/PNET

CHORDOMA

Location:

-sacral, coccygeal

-sphenooccipital (clivus, most common)

-cervical (chondroid chordomaà younger, better prognosis)

Gross: myxoid-blue and hemorrhagic

Micro: myxoid matrix with cords of small round cells with vacuolated cytoplasm, fibrous strands separating into tumour cells into lobules or cords

-physalipherous (bubbly) cells

Variants:

Chondroid chordomaàchondroid differentiation, better prognosis (cervical)

Dedifferentiated chordomaà differentiation into high grade spindle lesion

CHONDROBLASTIC TUMOURS

ENCHONDROMA

• § Clin: hands/feet
• § -Do not involve cortex or soft tissue.
• § -check xray; no invasion
• § Gross: well circ, cartilaginous, pale blue
• § Micro: hypocellular chondroid matrix with few doubly nucleated cells except in hands and feet.  (ddx. chondrosarcoma) May have reactive bone
• § Associated syndromes:
• § Ollier’s multiple ~,
• § Maffuci’s multiple ~ and soft tissue hemangiomas (risk of ovarian ca and gliomas)
• § Ddx: low grade chondrosarcoma
• § Clin: aka. Exostoses, young males @ metaphyses
• § Gross: sessile or pedunculated
• § Micro:
• § 1fibrous cap (continuous w/ perichondrium),
• § 2cartilage (endochondral ossification at interface),
• § 3bone
• § -can get secondary chondrosarcoma
• § Ddx: secondary chondrosarcoma, parosteal osteosarcoma (LG spindle cells b/w trabeculae)

OSTEOCHONDROMA

 

CHONDROBLASTOMA

• § Clin: epiphysis near knee, adolescents, painful
• § Gross: WC, white and firm; may have secondary ABC
• § Micro: giant cells, mononuclear cells with longitudinal grooves, chicken wire calcification, mitoses
• § Prog: usually benign
• § Clin: young adule @ metaphysis, long bones + small bones of the feet
• § Gross: small, cartilaginous
• § Micro: low power→lobulated due to: hypocellular chondro(in lacunae) / myxoid (stellate shape with atypia) foci  + adjacent cellular foci + GC (at periphery), much atypia
• § Prog: benign, but may have local recurrence
• § Clin: male adults, metaphysis in pelvis and shoulder girdles, painful
• § Gross: cartilaginous with myxoid change, cystic, necrosis
• § Micro: crowded, doubly nucleated, hyperchromatic +/- metaplastic bone formation +/- GC
• § Grade: based on cellularity and nuclear changes

CHONDROMYXOID FIBROMA

CHONDROSARCOMA

Name FIVE variants:

• § conventional
• § dedifferentiated chondrosarcoma: (abrupt transition)
• § m/chondrosarc + spindle cells (MFH, FS, OS);
• § mesenchymal chondrosarcoma: (abrupt) ribs/jaws young adults;
• § g/pink and fleshy;
• § m/small round blue cells + to well-diff cartliage;
• § clear cell chondrosarcoma: epiphysis,
• § -clear cytoplasm with nuclei with prominent nucleoli;
• § secondary chondrosarcoma: can rarely arise from osteochondromas and enchondromas
• § -usu low grade tumours
• § IHC: S100
• § Ddx: chondroblastic osteosarcoma (osteoid), enchondroma (no invasion, low grade)

 

FIBROBLASTIC AND CYSTIC LESIONS

FIBROUS DYSPLASIA

• § Clin: teens, medulla in the diaphysis of ribs, tibia, femur
• § -monoostotic or polyostotic(Albright synd, have cutaneous hyperpigtn)
• § Gross: firm and fibrous
• § Micro: hypocellular fibroblast spindle cells with + metaplastic bone formation “C” spicules w/ little osteoblastic rimming
• § -identical to fibrous dysplasia but occurs in the cortex of long bones…although may have more prominent osteoblastic rimming

OSTEOFIBROUS DYSPLASIA

 

NON-OSSIFYING FIBROMA/FIBROUS CORTICAL DEFECT

• § Clin: controversy as to whether or not a true neoplasm
• § -metaphysis of long bones.
• § Gross: well circ, red granular
• § Micro: spindle cell in storiform arrangement with GC, occ. mitoses, no atypia

 

ANEURSYMAL BONE CYST

• § Clin: kids, metaphysis and epiphysis
• § Gross: lytic lesion with periosteal rxn
• § cysts filled with blood, septae (contain fibroblasts, GC, bv)
• § Ddx: telangiectatic osteosarcoma, giant cell tumour of bone, giant cell reparative granuloma (if in jaw)

 

SOLITARY (UNICAMERAL) BONE CYST

• § Clin: boys in upper humerus or femur
• § Gross: straw/blood tinged fluid
• § Micro: fibroblasts, bv, hemosiderin
• § Tx: curretage and replacement with bone chips

 

OTHERS

LANGERHANS CELL HISTIOCYTOSIS /EOSINOPHILIC GRANULOMA

• § Clin: boys in flat/long bones in meta/diaphysis
• § Types: solitary or multiple bone lesion + other organs (skin, bone, liver, spleen);
• § Gross: sharply circumscribed
• § Micro: Langerhans cells (polygonal cells with eosinophilic cytoplasm, oval nuclei with longitudinal grooves resembling coffee beans),ef, GC, nf, foam cells, lf, pf, fibrosis, necrosis; mitoses
• § Etio
• § Unknown
• § Imaging***
• § “Hole-in-hole” in skull (due to unequal destruction of the two bone tablets)
• § What about lung?
• § Locations
• § Skull (no1) in kids vs ribs in adults
• § Solitary in lung (50%).
• § Nature
• § Neoplastic
• § Prognosis
• § Staging (can be very aggressive).
• § Internal organ involvement (marrow, liver, spleen, lungs) implies worse prognosis (can be fatal) although some may spontaneously resolve (Rapini)
• § Gross
• § Sharly circumscribed dark brown lesion (Rosai)

3 variants

• § Monostotic (eosinophilic granuloma) (no1)
  • Ø Older children and young adults[1], more benign course, mostly in bone (very rare in skin), less epidermotropism, fewer foamy cells, more diffuse infiltrate with MORE EOSINOPHILS, histocytes and giant cells (Rapini).
  • Ø Imaging: lytic in metaphysis of long bones +/- periosteal reaction (Rosai). Often confused with metastatic carcinoma or Ewing (Rosai).
  • Ø Locations: single bone but can be any except hands and feet (Rosai). Mostly cranial vault, jaw, humerus, rib and femur (Rosai). Bones of KIDS and adults (WHO; mainly in KIDS, Rapini). Strong predilection for jaws, especially mandible (Rosai)
  • Ø Outcome: spontaneous regression possible (Rosai). Excellent prognosis and rather excellent to develop lesions in other bones (Rosai)
  • Ø Spread: soft tissue extension when reccurs or after surgery (Rosai)
  • Ø Treatment: cured with low-dose radation because extremely radiosensitive (Rosai)
• § Polyostotic (Hand-Schuller-Christian)
  • Ø Adults, less epidermotropism, more giant cells, more foamy cells (Rapini).
  • Ø Caveat: Hand-Schuller-Christian disease defined as Langerhans histiocytosis, exophthalmos, diabetes insipidus (Osler)
  • Ø Outcome: prolonged with remission and relapse (Rosai). Still good prognosis (Rosai)
  • Ø Ssx: proptosis, diabetes insipidus, chronic ostitis media (Rosai)
• § Multiorgan (Letter-siwe disease)
  • Ø More in young infants, more fulminant, more epidermotropism and fewer foamy cells (Rapini)
  • Ø Demo: infants (<2) without sparing adults (WHO)
  • Ø Locations: polyostotic bones, skin and lung most common (Rosai). Also LN, stomach, thymus, CNS, thyroid, and all possible (WHO, Rosai). Any bone possible (mostly calvarium, ribs, femur) (Robbins).
  • Ø Outcome: rapidly fatal if not treated (WHO)
  • Ø Ssx: florid seborrheic eruption (Langerhans cells infiltrate over upper torso, HSM, LN, pulmonary lesions, destructive bone lesions (Robbins). Quite fulminant (Rapini). PRURITIC, SEBORRHEIC DERMATITIS-like lesions, especially on scalp, trunk and intertriginous areas (Rapini). Skin lesions can be solitary or multiple (Rapini)
  • Ø Lab: marrow infiltration leading to anemia, thrombocytopenia, infections (otitis, mastoiditis) (WHO).
  • Ø Treatment: must use chemotherapy.

3 patterns

• § Aggregates of similar cells resembling granulomas
• § Dermal infiltrate of foamy, xanthoma-like histiocytes (Robbins)
• § Diffuse dermal infiltrate of large, bland cells containing round/oval cleaved nuclei with pale pink cytoplasm admixed with eosinophils

• § Ddx
• § GCT of bone (me): I got fooled by one slide
• § Osteomyelitis, acute (AFIP; Rosai): similar inflammatory mixture, but no Langerhans’ cells, presence of capillary proliferation (absent in histiocytosis). If doubt, just do immuno. Careful, do not mistake eosinophils for neutrophils (study slide).
• § Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman) (Rosai; Steinberg): can involve bone, predominant plasma cells and histiocytes

 

 

LYMPHOMA

METASTATIC CARCINOMA

 

OTHER PRIMARY BONE LESIONS

ANGIOSARCOMA

HEMANGIOPERICYTOMA

BENIGN FIBROUS HISTIOCYTOMA

MALIGNANT FIBROUS HISTIOCYTOMA

DESMOPLASTIC FIBROMA

FIBROSARCOMA

GANGLION CYST

CYST OF DEGENERATIV JOINT DISEASE

FRACTURE CALLOUS

OSTEOMYELITIS

PAGET DISEASE

MASTOCYTOSIS

CHEST WALL HAMARTOMA

SYNOVIAL CHONDROMATOSIS

BONE INFARCT

NEUROPATHIC JOINT