Tumor like lesions of bone

Tumor like lesions of bone

Classification of bones

Structure of long bone

Short bones

• The significance of the tumor-like bony lesions is that their appearance may mimic that of malignant bone tumors, which gives rise to differential diagnostic problems, since they are 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 and

calcaneus (short bone).

• Some investigators have shown that the fluid has a biochemical composition similar to that of serum, suggesting that it forms from venous obstruction and subsequent extravasation of blood.

• Gross-

• Most are centered in metaphysis and they migrate away from epiphysis.

• Well delineated cyst filled with straw colored or blood stained serous fluid and is lined by smooth brown fibrous membrane.

• Cortex in thinned out.

• Periosteal bone proliferation in areas of fracture only.

• Fracture- Haemorrhagic fluid.

Gross appearances of solitary bone cyst. A triangular lesion located in the upper end of the tibia. There has been secondary hemorrhage, leading to an appearance not too dissimilar to that of an aneurysmal bone cyst.

Gross appearances of solitary bone cyst. A large lesion located in the upper metaphysis of the humerus.

• Microscopy-

• Cyst wall lacks true cell lining.

• And consists of thin layer of fibrous tissue, composed of scattered fibroblasts, collagen fibers, fibrin deposits, which can undergo mineralization and resemble cementum.

• In case of previous pathologic fracture- Cyst wall may be thickened and may contain reactive fibroblasts, osteoclast type giant cells, haemosiderin deposits and reactive woven bone.

Typical solitary bone cyst of upper end of humerus abutting against 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 the vertebrae, flat bones and shaft of long bones.

• Exceptions-• Osseous ABC in a soft tissue locations and within the wall

of major artery.

• ABC may arise denovo- Primary ABC.

• Or areas resembling ABC can be found in other benign and malignant bone tumors- Secondary ABC such as in association with

GCT of bone. Chondroblastoma. Osteoblastoma. Fibrous dysplasia and osteosarcoma.

Pathogenesis• Elusive.• Occasionally:

preceding trauma with fracture or subperiosteal hematoma.

preexisting bone lesion as result of changed hemodynamics.

• Usually no underlying lesion.might be result of sampling or cyst destruction of

preexisting lesion• Insulin-like growth factor-1.• Nonrandom cytogenetic aberrations suggest that

some are true neoplasms (17p11-13, 19q22).

• Grossly-• Multiple blood filled cystic spaces separated by thin

tan white septa.• Solid tan white areas- Either represents a solid

portion of ABC, or a primary lesion that has developed secondary ABC like change.

• X-ray-• Lytic, involves metaphysis of long bones, is eccentric

and shows blow-out appearance with extension into soft tissues.

• Periosteal new bone formation.

Aneurysmal bone cyst of lower end of ulna. The large blood-filled cavities expand the metaphysis.

Radiographic appearance of aneurysmal bone cyst of lower end of

fibula.

Aneurysmal bone cyst of ulna

• Microscopy-

• Large spaces: • filled with blood• no endothelial lining• delimited by cells:

with morphologic, ultrastructural, and immunohistochemical 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 fibromyxoid tissue: 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 giant cells. The intervening stroma is cellular but contains no neoplastic osteoid.

Aneurysmal bone cyst with multiple large giant cells and reactive bone at the periphery.

Solid Variant Of Aneurysmal Bone Cyst

• Features of ABCs in association with solid areas composed of: fibrous tissuenew bone formationosteoclasts

• Sometimes solid areas with this mixed appearance are seen 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.

Differential diagnosis

• Solitary Bone Cyst.

• Telengiectatic osteosarcoma.

• Giant cell reparative granuloma.

Metaphyseal fibrous defect

• It is a non-neoplastic process, possibly related to defect in ossification.

• Occurs under the age of 10 years.• Classically involves metaphysis in skeletally immature individuals.• Fibrous cortical defect- When confined to cortex.• Lesion enlarges and extends into the adjacent

medullary cavity- Non-ossifying fibroma.

• Sites- Distal femur, proximal and distal tibia.• Associated syndromes- Neurofibromatosis and Jaffe

Campanacci syndrome.• Asymptomatic and are discovered incidentally.

• Grossly-

• Lesion is tan brown on color with areas of yellow discoloration.

• Cystic changes may be present.• Haemorrhage and necrosis due to pathological

fracture.

• X ray-

• Eccentric, lytic lesion centered within the metaphyseal cortex and adjacent medullary cavity of long tubular bones.

• Well demarcated with sclerotic margins with internal trabeculations.

• Trabeculations are incomplete and are the result of scalloping of the affected cortex.

• As the patient grows, the lesion becomes incorporated into the diaphysis.

Metaphyseal fibrous defect of lower end of tibia.

Sharp delineation and sclerotic margins.

Large metaphyseal fibrous defect expanding lower tibial metaphysis.

Microscopy

• Spindle fibroblasts arranged in storiform pattern.

• Spindle cell have cytologically bland nuclei, that have pointed 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. There

are 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 may involve one or more bones.

• It has been likened to a localized developmental arrest- all components of normal bone are present but they do not differentiate into their mature structures.

Fibrous dysplasia variants

• Monostotic.• Polystotic.• Pauci-ostotic.• Monomelic.• Hemisomic.• Diffuse polystotic.• Albright syndrome.• Facial bone involvement.• Cherubism.• Leontiasis osseum.• Myxomas of soft tissue.• Mazabraud’s syndrome.

• Two forms:

• Monostotic: – More common and usually occurs in older children

and young adults.– most commonly affects rib, femur, tibia, jaw bones,

calvarium and humerus.– If craniofacial skeleton is involved disfigurement

occurs.– Monostotic disease does not evolve into the

polystotic form.

• Polyostotic .

• Manifests at slightly earlier age.• May be unilateral or bilateral.• Bones affected in decreasing order of frequency are

femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible and vertebrae.

• Craniofacial involvement in 50% of the cases and extensive skeletal disease in 100% patients.

• Have propensity to

involve shoulder and pelvic girdles, resulting in crippling deformities (Shepherd –crook

deformity of the proximal femur) and spontaneous, often recurrent fractures. Mazabraud syndrome- with soft tissue myxomas. McCune-Albright syndrome (2-3%)- Cafe-au-lait skin

pigmentation and endocrinopathies(sexual precocity, hyperthyroidism, pituitary adenomas that secrete GH and primary adrenal hyperplasia).

• Occurs due to somatic mutation occurring during embryogenesis that involves gene that codes for Guanine nucleotide binding protein (G protein).

• G protein normally couples receptors to the effector enzyme adenylyl cyclase and the mutation causes consecutive activation of the enzyme so that there is excess production of cyclic AMP, which leads to hyperfunction of cells in involved tissues.

• In bone this abnormality causes a proliferation of osteoprogenitor cells while at the same time inhibiting their differentiation.

• This leads to overproduction of fibrous matrix and woven bone formation.

• Grossly-

• Well circumscribed.• Gritty and leather like consistency.• Occasionally cystic areas may be seen.• In minority of cases nodules of pearly white cartilage

are seen.

Fibrous dysplasia of the rib. The lesion forms a fusiform, expanded mass that is grayish white.

• X ray-

• Classic groundglass appearance.• Can be radiolucent or radiodense depending on

amount of bone present and degree of mineralization.

• In appendicular skeleton- Well defined margins of the lesion and surrounded by rim of sclerotic bone.

• Craniofacial skeleton- less well defined and blends with 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 tip

of arrow).

Microscopy

• Cellular fibrous tissue surrounding irregular, curvilinear bony trabeculae.

• The bony trabeculae are discontinuous and are composed of woven bone that is formed directly from the spindle cells with minimal osteoblastic rimming.

• Fibrous tissue is composed of cytologically bland, plump spindle cells without atypia and mitotic figures.

• Spindle cells can be arranged in storiform pattern, in areas devoid of bone with collection of foamy histiocytes mimicking xanthoma/fibroxanthoma.

• Collagen fibers (Sharpey’s-like fibers) are seen extending from fibrous tissue into the lesional bone.

• Cellular nodules of hyaline or myxoid cartilage can be seen.

• Cartilage predominates- Fibrocartilagenous dysplasia.• Matrix ressembling cementum may be found in

lesions of cranio-facial skeleton.

Fibrous dysplasia

Fibrous dysplasia. Bone is woven and lacks osteoblastic rimming. Spindle cells are cytologically bland.

Differential diagnosis

• Desmoplastic fibroma.

• Osteofibrous dysplasia.

• Well-differentiated or low grade osteosarcoma.

Osteofibrous dysplasia

• It is a self limited benign fibro-osseous of bone characteristically involving cortical bone of the anterior mid-shaft of tibia during infancy and childhood.

• Also known as Kempson-Campanacci lesion or cortical 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 cortex

which in expanded and attenuated.

• Microscopy-• Irregular curvilinear trabeculae of woven bone,

which in the periphery merge with pre-existing lamellar cancellous bone.

• Trabeculae of woven bone is rimmed by osteoblasts.• Intervening stroma is composed of bland spindle

cells embedded within the collagenous matrix.

Osteofibrous dysplasiaGritty, tan white tumor expanding the fibula

Osteofibrous dysplasia. The low-power view is similar to that of fibrous dysplasia, but on high power there was osteoblastic rimming of the bone trabeculae.

Osteofibrous dysplasiaIt is composed of irregular trabeculae of woven bone

with prominent osteoblastic rimming

• X ray-

• Well delineated, intracortical lucency that is surrounded by areas of sclerosis which may extend into the medullary cavity.

• It may also manifest as multiple lytic foci scattered along the anterior cortex of tibia resulting in anterior bowing.

Osteofibrous dysplasiaOval lucencies with adjacent

sclerosis involving tibial diaphysis

• Differential diagnosis-

• Admantinoma.• Impossible to distinguish these tumors from

admantinoma on FNAC.• Histological confirmation is necessary.• Osteofibrous dysplasia is positive for vimentin, S-100

and Leu-7.• Isolated keratin positive mast cells have been

mentioned.• A tumor should be defined as OFD like admantinoma

when keratin positive epithelial cells are found.

Osteofibrous dysplasia Fibrous dysplasia

Common sites Tibia Femur, pelvis, ribs

Age 0-10 After 10 years

Bowing of tibia Frequent Absent

Spontaneous regression Possible Likely in monostotic cases

Tendency to reoccur before 10 years of age

High High if polystoticLow if monostotic

Progression during infancy and childhood

Moderate Variable but can be marked

Histology Zonal architecture: Lamellar bone peripherally, Woven bone centrally, Bone lined by osteoblasts, contiguous with cortex

Bone, usually without prominent osteoblast rimming, separated from cortex , woven bone

Molecular biology Not defined Mutations of the alpha subunits of the G- protein system

Myositis ossificans

• Myositis ossificans progressiva-• Very rare congenital progressive disease in which

groups of tendons and muscle, usually around major joints, become progressively calcified and ossified, producing severe functional disability.

• Microscopy reveal poorly organized bone, both lamellar 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 brown central area.

• Usually 2-5 cm in diameter and adherent to the surrounding muscle.

Well defined myositis ossificans occurring in the muscle

• Microscopy-

• In the central part of the lesion, an irregular mass of active mesenchymal cells with foci of interstitial haemorrhage.

• Haemosiderin laden macrophages.• Degenerative muscle fibers.• Whole lesion is intensely vascular, the vessels being

dilated channels lined by endothelium but without any formed media or adventitia.

• Small foci of osteoid production/cartilage can also be seen.

• At the periphery there are more clearly defined trabeculae.

• The bone is usually of the primitive woven type with large, round and crowded osteocytes.

• In long standing cases- Bone is mature and has a lamellar pattern.

• X ray-• Periosteal reaction and faint soft tissue calcification

within 3-6 weeks of injury.• Gradually replaced by mature heterotopic bone by

10-12 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 periphery and least mature at its center, the opposite is true of a soft tissue osteosarcoma.

Langerhan’s cell histiocytosis

• It is defined as an intraosseous mass of proliferating Langerhans cells.

• They are dendritic cells and normally populate the skin, mucosal surfaces, lymph nodes, where they function as antigen presenting cells.

• Single or multpile lesions restricted to the skeleton have 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, lung

and lymph nodes.• In skeleton most common- skull, jaw, vertebral

bodies, ribs, pelvis and long bones.

• 3 major categories-• Solitary bone involvement.• Multpile bone involvement (with or without skin).• Multiple organ involvement (Bone, liver, spleen and

others).

• Associated syndromes-

• Hand-Schuller-Christian disease-• Multifocal bone disease associated with exopthalmos

and diabetes insipidus.

• Letterer-Siwe disease- • Aggressive disseminated form of the disorder that

occurs 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 are arranged in aggregates, sheets or within loose fibrous stroma.

• Cells have eosinophilic cytoplasm and contain central, ovoid coffee bean shaped nuclei.

• Coffee bean appearance is produced by deep indentations, clefts and folds of the nuclear membranes which form linear grooves that traverse the length of the nuclei.

• Most of the Langerhan’s cells are mononuclear but some cells contain multiple nuclei, which tend to be centrally located.

• Accompanying infiltrate of eosinophils which may be so dense that it obscures underlying Langerhan’s cells.

• Lymphocytes, plasma cells, macrophages, neutrophils, osteoclast-type giant cells can also be seen.

• Necrosis if prominent is usually a complication of a pathologic fracture.

• Langerhans cells strongly express CD1a and S-100 protein.

This cell from Langerhans’ cell histiocytosis of bone contains several Birbeck's 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 a mild atypia in the Langerhans’ cells that can simulate a malignant process.

Langerhan’s cell histiocytosis

• X ray-

• Well defined, lytic lesions.• Cortical involvement may elicit periosteal reaction.

Langerhan’s cell histiocytosis.Osteolytic lesion of skull.

Langerhan’s cell histiocytosis

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 node and bone.

• Second and third decade of life.

• In bones- Skull, facial bones, ribs and vertebrae.

• X ray-• Well circumscribed radiolucency confined within the

bone without soft tissue or periosteal reactions.

Microscopy-• Heterogenous population of histiocytes,

lymphocytes, plasma cells and neutrophils which can form microabcsess like foci.

• Histocytes may demonstrate vacuolar cytoplasm and cellular phagocytosis (erythrophagocytosis and leukophagocytosis).

• Emperipolesis- Phagocytosis of RBCs, plasma cells/neutrophils is hallmark of disease.

• Differential diagnosis-

• Langerhan’s cell histiocytosis.• Lymphoma.• Osteomyelitis.• Storage disease.

Rosai–Dorfman disease. High-power view showing lymphocytophagocytosis by the sinus histiocytes.

References

• Rosai and Ackerman’s Surgical Pathology, Ninth edition.

• Silverberg’s Principles and Practice of Surgical Pathology and Cytopathology, fourth edition.

• Diagnostic Histopathology of tumors by Christopher Fletcher, third edition.

Thank you