• The significance of the tumor-like bony lesionsis that their appearance may mimic that ofmalignant bone tumors, which gives rise todifferential diagnostic problems, since theyare much more common.
Solitary bone cyst• It is a fluid filled cyst of unknown etiology.• Commonly in males under the age of 20.• Usually occurs in long bones.• Sites- Proximal humerus, proximal femur, pelvis andcalcaneus (short bone).• Some investigators have shown that the fluid has abiochemical composition similar to that of serum,suggesting that it forms from venous obstruction andsubsequent extravasation of blood.
• Gross-• Most are centered in metaphysis and they migrateaway from epiphysis.• Well delineated cyst filled with straw colored orblood stained serous fluid and is lined by smoothbrown fibrous membrane.• Cortex in thinned out.• Periosteal bone proliferation in areas of fracture only.• Fracture- Haemorrhagic fluid.
Gross appearances of solitary bonecyst.A triangular lesion located in theupper end of the tibia. There has beensecondary hemorrhage, leading to anappearance not too dissimilar to thatof an aneurysmal bone cyst.Gross appearances of solitary bonecyst.A large lesion located in the uppermetaphysis of the humerus.
• Microscopy-• Cyst wall lacks true cell lining.• And consists of thin layer of fibrous tissue, composedof scattered fibroblasts, collagen fibers, fibrindeposits, which can undergo mineralization andresemble cementum.• In case of previous pathologic fracture- Cyst wall maybe thickened and may contain reactive fibroblasts,osteoclast type giant cells, haemosiderin depositsand reactive woven bone.
Typical solitary bone cyst of upper end of humerus abuttingagainst epiphyseal plate complicated by fracture.(Soap bubble appearance).
• Diagnosis-• May be difficult if:– reparative changes following fracture.– recurrent lesion after bone grafting.– articular cartilage included in curettings.• Becomes clear if history and radiographs available.• Differential diagnosis-• Aneurysmal bone cyst.
Aneurysmal bone cyst• First described by Jaffe and Lichtenstein in 1942.• Seen in patients between 10-20 years of age.• Slightly common in females.• It is a cystic lesion of bone most common in thevertebrae, flat bones and shaft of long bones.• Exceptions-• Osseous ABC in a soft tissue locations and within the wallof major artery.
• ABC may arise denovo- Primary ABC.• Or areas resembling ABC can be found in otherbenign and malignant bone tumors- Secondary ABCsuch as in association with GCT of bone. Chondroblastoma. Osteoblastoma. Fibrous dysplasia and osteosarcoma.
Pathogenesis• Elusive.• Occasionally:preceding trauma with fracture or subperiostealhematoma.preexisting bone lesion as result of changedhemodynamics.• Usually no underlying lesion.might be result of sampling or cyst destruction ofpreexisting lesion• Insulin-like growth factor-1.• Nonrandom cytogenetic aberrations suggest thatsome are true neoplasms (17p11-13, 19q22).
• Grossly-• Multiple blood filled cystic spaces separated by thintan white septa.• Solid tan white areas- Either represents a solidportion of ABC, or a primary lesion that hasdeveloped secondary ABC like change.• X-ray-• Lytic, involves metaphysis of long bones, is eccentricand shows blow-out appearance with extension intosoft tissues.• Periosteal new bone formation.
Aneurysmal bone cyst of lower end of ulna.The large blood-filled cavities expand the metaphysis.
Radiographic appearance ofaneurysmal bone cyst of lower end offibula.Aneurysmal bone cyst of ulna
• Microscopy-• Large spaces:• filled with blood• no endothelial lining• delimited by cells:with morphologic, ultrastructural, andimmunohistochemical features of fibroblasts,myofibroblasts and histiocytes.these cells also occupy septa that separate the cysts.• row of osteoclasts often immediately beneath surface.• Deposition of peculiar degenerated calcifying fibromyxoidtissue: great diagnostic significance.• Septa also contains blood vessels, foci of osteiod and bone.
Aneurysmal bone cyst of lower end of ulna.It is showing two cavities lined by osteoclast-like multinucleated giantcells. The intervening stroma is cellular but contains no neoplastic osteoid.
Aneurysmal bone cyst with multiple large giant cellsand reactive bone at the periphery.
Solid Variant Of Aneurysmal Bone Cyst• Features of ABCs in association with solid areascomposed of:fibrous tissuenew bone formationosteoclasts• Sometimes solid areas with this mixed appearance areseen in the absence of typical ABC features.• Locations include:small bones of hand and feet, vertebrae, sacrum.less commonly long bones:• tend to have a metaphysical location.
Gross appearance of so-called ‘solid variant’ of aneurysmal bone cyst.A few hemorrhagic cystic areas are present at the periphery.
Metaphyseal fibrous defect• It is a non-neoplastic process, possibly related todefect in ossification.• Occurs under the age of 10 years.• Classically involves metaphysis in skeletally immatureindividuals.• Fibrous cortical defect- When confined to cortex.• Lesion enlarges and extends into the adjacentmedullary cavity- Non-ossifying fibroma.
• Sites- Distal femur, proximal and distal tibia.• Associated syndromes- Neurofibromatosis and JaffeCampanacci syndrome.• Asymptomatic and are discovered incidentally.
• Grossly-• Lesion is tan brown on color with areas of yellowdiscoloration.• Cystic changes may be present.• Haemorrhage and necrosis due to pathologicalfracture.
• X ray-• Eccentric, lytic lesion centered within themetaphyseal cortex and adjacent medullary cavity oflong tubular bones.• Well demarcated with sclerotic margins with internaltrabeculations.• Trabeculations are incomplete and are the result ofscalloping of the affected cortex.• As the patient grows, the lesion becomesincorporated into the diaphysis.
Metaphyseal fibrous defect oflower end of tibia.Sharp delineation and scleroticmargins.Large metaphyseal fibrous defectexpanding lower tibial metaphysis.
Microscopy• Spindle fibroblasts arranged in storiform pattern.• Spindle cell have cytologically bland nuclei, that havepointed ends and eosinophillic cytoplasm.• Osteoclast type giant cells.• Few mitosis.• Haemosiderin deposits and foamy macrophages.
Metaphyseal fibrous defect.The predominant element is a spindle cell of fibroblastic appearance. Thereare also irregularly scattered osteoclasts.
Fibrous dysplasia and related lesions• First described by Albright in 1937.• Most common of the fibro-osseous tumours.• It is a benign medullary fibro-osseous lesion which mayinvolve one or more bones.• It has been likened to a localized developmental arrest-all components of normal bone are present but they donot differentiate into their mature structures.
• Two forms:• Monostotic:– More common and usually occurs in older childrenand young adults.– most commonly affects rib, femur, tibia, jaw bones,calvarium and humerus.– If craniofacial skeleton is involved disfigurementoccurs.– Monostotic disease does not evolve into thepolystotic form.
• Polyostotic .• Manifests at slightly earlier age.• May be unilateral or bilateral.• Bones affected in decreasing order of frequency arefemur, skull, tibia, humerus, ribs, fibula, radius, ulna,mandible and vertebrae.• Craniofacial involvement in 50% of the cases andextensive skeletal disease in 100% patients.
• Have propensity to involve shoulder and pelvic girdles, resulting in crippling deformities (Shepherd –crookdeformity of the proximal femur) and spontaneous, often recurrent fractures. Mazabraud syndrome- with soft tissue myxomas. McCune-Albright syndrome (2-3%)- Cafe-au-lait skinpigmentation and endocrinopathies(sexual precocity,hyperthyroidism, pituitary adenomas that secrete GHand primary adrenal hyperplasia).
• Occurs due to somatic mutation occurring duringembryogenesis that involves gene that codes forGuanine nucleotide binding protein (G protein).• G protein normally couples receptors to the effectorenzyme adenylyl cyclase and the mutation causesconsecutive activation of the enzyme so that there isexcess production of cyclic AMP, which leads tohyperfunction of cells in involved tissues.• In bone this abnormality causes a proliferation ofosteoprogenitor cells while at the same timeinhibiting their differentiation.• This leads to overproduction of fibrous matrix andwoven bone formation.
• Grossly-• Well circumscribed.• Gritty and leather like consistency.• Occasionally cystic areas may be seen.• In minority of cases nodules of pearly white cartilageare seen.
Fibrous dysplasia of the rib.The lesion forms a fusiform, expanded mass that isgrayish white.
• X ray-• Classic groundglass appearance.• Can be radiolucent or radiodense depending onamount of bone present and degree ofmineralization.• In appendicular skeleton- Well defined margins ofthe lesion and surrounded by rim of sclerotic bone.• Craniofacial skeleton- less well defined and blendswith surrounding bone.
Fibrous dysplasia of tibia forming a sharply delimited lesion.
Fibrous dysplasia in the upper arm (humerus).Left, An X-ray showing fibrous dysplasia.Center, magnetic resonance image of the same area.Right, X-ray of the same bone one year later with a fracture (at tipof arrow).
Microscopy• Cellular fibrous tissue surrounding irregular,curvilinear bony trabeculae.• The bony trabeculae are discontinuous and arecomposed of woven bone that is formed directlyfrom the spindle cells with minimal osteoblasticrimming.• Fibrous tissue is composed of cytologically bland,plump spindle cells without atypia and mitoticfigures.
• Spindle cells can be arranged in storiform pattern, inareas devoid of bone with collection of foamyhistiocytes mimicking xanthoma/fibroxanthoma.• Collagen fibers (Sharpey’s-like fibers) are seenextending from fibrous tissue into the lesional bone.• Cellular nodules of hyaline or myxoid cartilage can beseen.• Cartilage predominates- Fibrocartilagenousdysplasia.• Matrix ressembling cementum may be found inlesions of cranio-facial skeleton.
Osteofibrous dysplasia• It is a self limited benign fibro-osseous of bonecharacteristically involving cortical bone of theanterior mid-shaft of tibia during infancy andchildhood.• Also known as Kempson-Campanacci lesion orcortical fibrous dysplasia.• Occurs from 3 weeks to 35 years of life.• Associated with trisomy 7 and 8.
• Gross-• < 1cm to > 10 cm• Solid, yellow-white, gritty and centered in cortexwhich in expanded and attenuated.• Microscopy-• Irregular curvilinear trabeculae of woven bone,which in the periphery merge with pre-existinglamellar cancellous bone.• Trabeculae of woven bone is rimmed by osteoblasts.• Intervening stroma is composed of bland spindlecells embedded within the collagenous matrix.
Osteofibrous dysplasiaGritty, tan white tumor expanding the fibula
Osteofibrous dysplasia.The low-power view is similar to that of fibrousdysplasia, but on high power there was osteoblasticrimming of the bone trabeculae.
Osteofibrous dysplasiaIt is composed of irregular trabeculae of woven bonewith prominent osteoblastic rimming
• X ray-• Well delineated, intracortical lucency that issurrounded by areas of sclerosis which may extendinto the medullary cavity.• It may also manifest as multiple lytic foci scatteredalong the anterior cortex of tibia resulting in anteriorbowing.
Osteofibrous dysplasiaOval lucencies with adjacentsclerosis involving tibial diaphysis
• Differential diagnosis-• Admantinoma.• Impossible to distinguish these tumors fromadmantinoma on FNAC.• Histological confirmation is necessary.• Osteofibrous dysplasia is positive for vimentin, S-100and Leu-7.• Isolated keratin positive mast cells have beenmentioned.• A tumor should be defined as OFD like admantinomawhen keratin positive epithelial cells are found.
Osteofibrous dysplasia Fibrous dysplasiaCommon sites Tibia Femur, pelvis, ribsAge 0-10 After 10 yearsBowing of tibia Frequent AbsentSpontaneous regression Possible Likely in monostotic casesTendency to reoccurbefore 10 years of ageHigh High if polystoticLow if monostoticProgression duringinfancy and childhoodModerate Variable but can be markedHistology Zonal architecture: Lamellarbone peripherally, Wovenbone centrally, Bone linedby osteoblasts, contiguouswith cortexBone, usually withoutprominent osteoblastrimming, separated fromcortex , woven boneMolecular biology Not defined Mutations of the alphasubunits of the G- proteinsystem
Myositis ossificans• Myositis ossificans progressiva-• Very rare congenital progressive disease in whichgroups of tendons and muscle, usually around majorjoints, become progressively calcified and ossified,producing severe functional disability.• Microscopy reveal poorly organized bone, bothlamellar and woven and dense fibrous scar tissue.• Poorly formed cartilage can also be seen.
• Myositis ossificans circumscripta-• Patients present with lump is muscle.• History of trauma in only half of the patients.• Common locations- flexor muscles of the upper arm,quadriceps femoris, adductor muscle of the thigh,gluteal muscles and soft tissues of the hand.
• Gross-• Shell of bony tissue with more or less soft red browncentral area.• Usually 2-5 cm in diameter and adherent to thesurrounding muscle.
Well defined myositis ossificans occurring in the muscle
• Microscopy-• In the central part of the lesion, an irregular mass ofactive mesenchymal cells with foci of interstitialhaemorrhage.• Haemosiderin laden macrophages.• Degenerative muscle fibers.• Whole lesion is intensely vascular, the vessels beingdilated channels lined by endothelium but withoutany formed media or adventitia.• Small foci of osteoid production/cartilage can also beseen.
• At the periphery there are more clearly definedtrabeculae.• The bone is usually of the primitive woven type withlarge, round and crowded osteocytes.• In long standing cases- Bone is mature and has alamellar pattern.• X ray-• Periosteal reaction and faint soft tissue calcificationwithin 3-6 weeks of injury.• Gradually replaced by mature heterotopic bone by10-12 weeks.
Myositis ossificans.Deep region showing a highly cellular appearance
Myositis ossificans.Peripheral portion showing a shell of well-formed bone.
Myositis ossificans.Midportion showing osteoid formation by plump osteoblasts.
Differential diagnosis• Sarcoma.• Myositis ossificans is most mature at its peripheryand least mature at its center, the opposite is true ofa soft tissue osteosarcoma.
Langerhan’s cell histiocytosis• It is defined as an intraosseous mass of proliferatingLangerhans cells.• They are dendritic cells and normally populate theskin, mucosal surfaces, lymph nodes, where theyfunction as antigen presenting cells.• Single or multpile lesions restricted to the skeletonhave been termed as eosinophilic granuloma.
• Common during first three decades of life.• Males are affected more than females.• The disease usually manifests in skeleton, skin, lungand lymph nodes.• In skeleton most common- skull, jaw, vertebralbodies, ribs, pelvis and long bones.• 3 major categories-• Solitary bone involvement.• Multpile bone involvement (with or without skin).• Multiple organ involvement (Bone, liver, spleen andothers).
• Associated syndromes-• Hand-Schuller-Christian disease-• Multifocal bone disease associated with exopthalmosand diabetes insipidus.• Letterer-Siwe disease-• Aggressive disseminated form of the disorder thatoccurs in infants.
• Gross-• Non-specific, gritty, tan appearance.• Microscopy-• The proliferating Langerhan’s cells are ovoid/round,histiocyte like cells, 10-15 um in diameter that arearranged in aggregates, sheets or within loosefibrous stroma.• Cells have eosinophilic cytoplasm and containcentral, ovoid coffee bean shaped nuclei.
• Coffee bean appearance is produced by deepindentations, clefts and folds of the nuclearmembranes which form linear grooves that traversethe length of the nuclei.• Most of the Langerhan’s cells are mononuclear butsome cells contain multiple nuclei, which tend to becentrally located.• Accompanying infiltrate of eosinophils which may beso dense that it obscures underlying Langerhan’scells.
• Lymphocytes, plasma cells, macrophages,neutrophils, osteoclast-type giant cells can also beseen.• Necrosis if prominent is usually a complication of apathologic fracture.• Langerhans cells strongly express CD1a and S-100protein.
This cell from Langerhans’ cell histiocytosis of bonecontains several Birbecks granules (arrows)
Langerhan’s cell histiocytosis of skull.A sharp, well circumscribed, dark brown lesion is seen.
Langerhans’ cell histiocytosis.Polymorphic appearance resulting from an admixture of Langerhans’cells, nonspecific histiocytes, lymphocytes, and eosinophils. There is amild atypia in the Langerhans’ cells that can simulate a malignantprocess.
Differential diagnosis• Osteomyelitis .• Hodgkin’s disease.• Malignant lymphoma.• Osseous manifestations of Rosai-Dorfman’s disease.• Fungal/parasitic infections.• Foreign body giant cell reactions.• Metastatic carcinoma and Ewing’s sarcoma(Radiologically).
Poor prognostic factors• Young age (< 18 months).• Hepatomegaly.• Anaemia.• Thrombocytopenia.• Bone marrow involvement.• Haemorrhagic skin lesions.
Rosai-Dorfman’s disease• Sinus histiocytosis with massive lymphadenopathy.• Involves skin, upper respiratory tract, lymph nodeand bone.• Second and third decade of life.• In bones- Skull, facial bones, ribs and vertebrae.
• X ray-• Well circumscribed radiolucency confined within thebone without soft tissue or periosteal reactions.Microscopy-• Heterogenous population of histiocytes,lymphocytes, plasma cells and neutrophils which canform microabcsess like foci.• Histocytes may demonstrate vacuolar cytoplasm andcellular phagocytosis (erythrophagocytosis andleukophagocytosis).• Emperipolesis- Phagocytosis of RBCs, plasmacells/neutrophils is hallmark of disease.
References• Rosai and Ackerman’s Surgical Pathology,Ninth edition.• Silverberg’s Principles and Practice of SurgicalPathology and Cytopathology, fourth edition.• Diagnostic Histopathology of tumors byChristopher Fletcher, third edition.