• Benign tumors of bone
• Malignant tumors of bone
• Primary bone tumors are rare;
• Non-neoplastic conditions, metastatic disease, and
lymphohematologic malignancies, which may simulate
primary bone tumors, by far outnumber genuine bone tumors.
• The classification of bone tumor is based on histologic criteria,
particularly on the type of differentiation shown by tumor cells
and the type of intercellular material they produce, as seen by
conventional light microscopy.
• However, it is recognized that electron microscopy and especially
immunohistochemical techniques may be relevant for precise
classification and diagnosis in specific instances.
• The final diagnosis of bone tumors should be based on a
synthesis of histopathologic findings, clinical presentation,
and imaging characteristics.
Predominant tissue Benign Malignant
Bone forming Osteoma
Osteoid osteoma and
Cartilage forming Chondroma
-Clear cell chondrosarcoma
Marrow tumors -Ewing sarcoma
-Primitive neuroectodermal tumor of
-Malignant lymphoma of bone
WHO Histologic Classification of Bone Tumors 1993
• A benign central tumor composed of mature cartilage, is a well-
recognized entity in certain areas of the bony skeleton
• Considerable clinical importance because of the propensity of the
tumor to undergo malignant degeneration in some instances, even
after remaining quiescent for long periods of time.
• Types: A) Central chondroma / Enchondroma- develop within
• B) Periosteal chondroma / Ecchondroma - develops on the surface
• C) Soft tissue chondroma.
• Develop at any age and
• Shows no apparent gender predilection
• Site: maxilla: anterior portion of the maxilla
mandible: posterior to the cuspid tooth, involving the
body of the mandible, the coronoid or condylar processes.
• c/p: arises as a painless, slowly progressive swelling of the
jaw, may cause loosening of the teeth
• Destructive lesion
• Irregular radiolucent or mottled area in the bone
• Root resorption of teeth adjacent to it
• Chondroma is made up of a mass of hyaline cartilage which
may exhibit areas of calcification or of necrosis.
• The cartilage cells appear small, contain only single nuclei and
do not exhibit great variation in size, shape or staining reaction.
• vary considerably in appearance from area to area.
A, Chondroma. Strands of epithelium-like cells with abundant eosinophilic cytoplasm
reside in a blue-gray mucinous stroma. B, Area of chondroma with tumor cells showing
cytoplasmic vacuolation with the formation of multivacuolated physaliferous cells.
A, Enchondroma shows small, uniform chondrocytes whose nuclei are densely
hyperchromatic (ink dot) without a visible chromatin pattern. Cells are well separated from
each other. B, An island of hyaline cartilage in an enchondroma is separated from the
adjacent bone trabeculae by a zone of normal marrow tissue
• Osteoma is a benign neoplasm characterized by a
proliferation of either compact or cancellous bone,
usually in an endosteal or periosteal location.
• Described as a specific entity by Jaffe in 1935
• Occurs almost exclusively in the head and neck region
• Not a common oral lesion.
Compact osteoma: consists of compact bone, which has a dense
lamellae of bone
Cancellous osteoma: consisting of trabeculae of bone
Periosteal, peripheral or exophytic osteoma: arise on the
surface of bone as sessile mass
Endosteal or central osteoma: located in the medullary bone
Osteoma cutis: extraskeletal lesion of soft tissue seen in the
dermis of the skin
• Age: second to fourth decades of life,
• males> female
• c/p: slow growing tumor.
• Periosteal origin → circumscribed swelling → obvious asymmetry.
• Endosteal origin → expansion of the cortical plates.
• Multiple osteomas of the jaws, as well as of long bones and skull,
are a characteristic manifestation of Gardner syndrome.
• It is an autosomal dominant disorder.
• Mutation in APC gene
• characterized by the triad of colonic polyposis, multiple
osteomas and mesenchymal tumors of the skin and soft tissues
including epidermal inclusion cyst, lipoma, fibroma, and
• Multiple odontomas, Compound odontomas
• Supernumerary teeth
• Impacted permanent teeth
• One or more osteomas of the jaws
• Occult radiopaque lesions of the jaws are common
• Various incidental findings include hypercementosis, root
resorption, ankylosis and persistent primary teeth.
• Composed either of extremely dense, compact bone or of
coarse cancellous bone.
• Bone formed appears normal
• Well circumscribed.
• In some tumors foci of cartilage may be found, in which
case the term ‘osteochondroma’ is often used.
• Myxomatous tissue also may be intermingled on rare
Compact and trabecular bone is present beneath intact mucosa at the left of the field.
B, Compact cortical-type bone of the osteoma shown in A contains haversian systems
Treatment and Prognosis
• Symptomatic lesions→ local excision.
• No recurrence after surgical removal.
• Benign tumor of bone, seldom been described in the jaws.
• True nature → unknown.
• Jaffe and Lichtenstein have suggested “A true neoplasm of
• Age: young persons, under the age of 10 years
• Sex: males:female - 2:1.
• Site: Frequently in the femur or in the tibia.
• In head and neck→ Cervical spine > mandible and maxilla.
• Chief symptoms → severe pain → unrelenting and sharp, worse at
• Classically, the pain is relieved by aspirin.
• In its active growth phase
• Grossly appears as a discrete, round to oval lesion marked by a
cherry-red or reddish-brown color. Quite granular and friable and
easily displaced from the adjacent bone.
• In its mature phase → more calcification and bone production, the
lesion is hard and gritty and blends with the bone around it.
• Characteristic and consists of a central nidus composed of compact
osteoid tissue, varying in degree of calcification, interspersed by a
vascular connective tissue.
• Formation of definite trabeculae occurs, particularly in older
lesions, outlined by active osteoblasts.
• Osteoclasts and foci of bone resorption are also usually evident.
• Overlying periosteum exhibits new bone formation, and in this
interstitial tissue collections of lymphocytes seen.
A, Nidus of osteoid osteoma abuts thickened mature bone. B, Osteoid trabeculae, some
partially calcified, within the nidus of an osteoid osteoma. The trabeculae are rimmed with
plump osteoblasts with occasional osteoclasts. The stroma is hemorrhagic.
Ultrastructural investigation by Steiner,
• The morphology of the osteoblasts to be similar to that of
• Although atypical mitochondria could be seen.
• Neural staining → many axons throughout an osteoid osteoma,
which probably accounts for the pain (the nidus).
• ↑Levels of prostaglandin E2 in the nidus; this is presumably
the cause of pain and vasodilatation.
(Giant osteoid osteoma)
• Osteoblastoma accounts →1% of primary bone tumors.
• It is typically a slow-growing, benign bone tumor.
• Incidence in the head and neck → 13% to 26%.
• Osteoblastoma frequently lacks the characteristic pain and the
halo of sclerotic bone associated with osteoid osteoma.
• Benign osteoblastoma → Jaffe and by Lichtenstein in 1956.
• Jaffe and Lichtenstein stated this lesion to be “a true neoplasm
of osteoblastic derivation”.
• Abnormal local response of the tissues to injury, and
• Local alteration in bone physiology
• Age: in young persons, 20-30 years.
• Sex: Males>Females.
• C/P: characterized clinically by pain and swelling.
pain → more generalized and less likely relieved by salicylates.
• Most common site → vertebral column.
• Mandible > Maxilla
• Occurs in Periosteal, cortical, or medullary location
On gross examination,
• Well delimited within either the cortex
or cancellous bone.
• Gritty or granular consistency with
The hallmark of the benign osteoblastoma consists of:
The vascularity of the lesion with many dilated capillaries
scattered throughout the tissue
The moderate numbers of multinucleated giant cells scattered
throughout the tissue, and
The actively proliferating osteoblasts which pave the
irregular trabeculae of new bone
It may or may not have a central sclerotic nidus
• In the less mature lesion → abundance of connective tissue
stroma in which osteoclast-type giant cells and small foci of
osteoid are present, some in a lacelike pattern.
• With maturation → progressive mineralization of the osteoid
with conversion to trabeculae of coarse woven bone, rimmed by
plump osteoblasts. The trabeculae may fuse to form an
anastomosing, netlike pattern.
• The osteoblasts usually lack any significant atypia, having
round to oval regular nuclei, often with prominent nucleoli.
Mitotic activity is infrequent.
• The combination of bone production and resorption → pagetoid
- appearing bone with prominent cement lines
A, Nidus of osteoblastoma shows active production of osteoid trabeculae, some in the early stage
of bone formation. The trabeculae are lined with enlarged osteoblasts with occasional osteoclasts.
Numerous dilated capillaries are present in the stroma. B, Large epithelioid osteoblasts, in
osteoblastoma, have abundant cytoplasm and large nuclei containing prominent nucleoli.
Formation of lacelike osteoid is seen.
Osteoblastoma comprises interanastomosing
trabeculae of woven bone lined by a single
layer of osteoblasts within a loosely textured
The nidus is formed by dense sclerotic
irregular or mosaic-like reversal lines
indicative of active remodeling similar to
that seen in Paget disease
Tumor trabeculae frequently
connect with the surrounding bone
Extensive intralesional hemorrhage
Parallel arrays of sclerotic bone that
radiate away from center
It is primarily defined by epithelioid osteoblasts,
cells with abundant eosinophilic cytoplasm twice
the size of conventional osteoblasts. These cells
are frequently arranged in sheets with little or no
Cytologically, the neoplastic osteoblasts have
abundant basophilic, finely granular cytoplasm
with a perinuclear holo of less dense cytoplasm
and an eccentric vesicular nucleus with a solitary
• Osteoid osteoma
• Aneurysmal bone cyst
• Osteoblastoma like Osteosarcoma
Treatment and Prognosis:
• Conservative surgical excision
• Recurrence is rare.
• Osteochondroma or solitary osteo-cartilaginous exostosis is an
exophytic lesion that arises from the cortex of bone and is capped
• 35%-50% of all benign bone tumors
• 8%-15% of all primary bone tumors
• Occurs frequently in the metaphyseal region of the long bones
• Osteochondroma can eventually transform into a secondary peripheral
chondrosarcoma in 1–3% of patients with multiple osteochondromas.
• Different theories of etiopathogenesis proposed:
• Age- 13-78 years, mean age- 38.4 years
• Sex: females> males
• Site: coronoid process and the mandibular condyle are the affected.
Especially the medial aspect of the mandibular condyle.
• slow growing.
• facial asymmetry, malocclusion, cross-bite on contra-lateral side
and lateral open-bite on the affected side, deviation on opening,
hypomobility, pain and clicking
A, Peripheral portion of osteochondroma shows a cartilage cap covered by a layer of
periosteum (perichondrium). Active enchondral ossification is present, with widely dilated
capillaries present at the base of the cartilage. The marrow is filled with fat. B, Bone within
osteochondroma shows persistence of partially ossified hyaline cartilage within the centers of
OSTEOSARCOMA / OSTEOGENIC SARCOMA
• Osteosarcoma is the third most common cancer in
adolescence, occurring less frequently than only
lymphomas and brain tumors.
• It is thought to arise from a primitive mesenchymal bone-
forming cell and is characterized by production of osteoid
• Irradiation : 2% of osteosarcomas.
• pre-existing benign bone disorders –
bone dysplasia, fibrous dysplasia, Pagets disease
• Disturbance of bone growth and maturation -
corresponds with growth spurt
• Environmental factors:
Ultraviolet and ionising radiation
Viral origin: simian virus 40 (SV40)
• Transcription Factors
Excess production of transcription factors, or the production of a
new overactive transcription factor, may result from gene
Overexpression of Myc
• Growth Factor
Dysregulated expression of growth factors such as TGF, IGF, and
CTGF leads to the accelerated proliferation of cells.
• Genetic predisposition
Alterations in genetic pathways including Rb, p53, SAS (sarcoma
Protein expression of the defective/amplified genes results in loss of
control of cell proliferation and differentiation
• Syndromes – Li-Fraumeni syndrome
- Rothmund-Thompson syndrome
Classification of osteosarcoma
• Conventional-sub-typed as:
• Small cell
• Intraosseous well differentiated and Intracortical
• Surface osteosarcomas:-Parosteal, Periosteal, High grade surface
• Secondary osteosarcomas
Paget’s disease and after radiation exposure.
• Unusual forms of osteosarcoma subtypes of conventional
osteosarcoma because their biological behavior is similar.
Osteoblastic osteosarcoma-sclerosing type
Osteosarcoma resembling osteoblastoma
Chondromyxoid fibroma-like osteosarcoma
Malignant fibrous histiocytoma-like osteosarcoma
Giant cell rich osteosarcoma
• Sex- M>F
• Age – 3rd and 4th decade
• Site - metaphysial growth plates of extremities of long bones
• femur>tibia>humerus>skull or jaw>pelvis
• Mandible : Maxilla = 1.5:1
• Mandible: body of the mandible > symphysis > angle of the
mandible > ascending ramus >TMJ.
• Osteoblastic - white-tan, yellow in color, firm in consistency
• Chondroblastic - translucent lobules
• Fibroblastic - tan colored with soft or firm in consistency
• Presence of osteoid formation by malignant osteoblasts
• Stromal cells are spindle shaped and atypical with
irregularly shaped nuclei
• The amount of matrix material produced in the tumor
• Mitotic activity with frequent abnormal forms
• Depending on the relative amounts of osteoid, cartilage.
or collagen fibers produced by the tumor.
• Atypical neoplastic osteoblasts that exhibit variation in size and shape
• large deeply staining nuclei arranged in disordered fashion about
trabaculae of bone .
• Irregular pattern or solid sheets of new tumor osteoid and bone
• Fibroblastic type- varying degrees of proliferation of anaplastic
fibroblasts, absence of tumor osteoid.
• Occasional areas of neoplastic myxomatous tissue and cartilage.
• Comprised about 34%
• Chondroblastic- currently believe that even though a lesion is
composed chiefly of malignant cartilage, it should be diagnosed
as osteosarcoma, if significant malignant osteoblasts and tumor
osteoid or bone can be identified since the course of the lesion
will probably be that of an osteosarcoma rather than of a
Lacelike streamers of pink osteoid
produced by malignant stromal cells
Area in a conventional
osteosarcoma shows a combination
of osteoid, malignant cartilage, and
spindle cell fibrous zones
Telangiectatic osteosarcoma resemble an
aneurysmal bone cyst. Blood filled cystic
spaces are separated by delicate septa.
Benign giant cells resembling osteoclasts
are seen in about 25% of osteosarcomas.
• Long bone involvement→ amputation is a prime requisite.
• Radical resection
• Primary X-ray radiation is of no avail.
• Preoperative chemotherapy →facilitate subsequent surgical removal
by shrinking the tumor.
• Adjuvant chemotherapy in combination with surgery, including
resection of pulmonary metastases, has appeared to offer promise of
increased survival from this disease
• Overall 5 years survival – 63%
• Chondrosarcoma is a malignant tumor characterized by the
formation of cartilage.
• Comprise about 10% of all primary tumors
• 1 % to 3% arise in the head and neck area.
• Primary: arise directly from the cartilage
• Secondary: develop in a pre-existing benign cartilaginous tumor.
• Age: 6th- 7th decade
• No significant sex predilection
• Site: In head and neck→ maxilla, mandible, base of the skull,
cervical vertebrae, nasal cavity and nasal septum.
• c/p: painless mass or swelling, loosening of teeth.
• Maxillary tumors may cause nasal obstruction, congestion ,
epistaxis, photophobia, or visual loss.
• On sectioning→ lobular, blue-gray to gray-white, translucent,
glistening surface, although firm, they are usually easily cut with a
scalpel, except for areas with dense calcification or ossification.
• Necrosis within the center of the lobules is common.
• Chondrosarcomas are composed of cartilage showing varying degrees
of maturation and cellularitywith typical lacunar formation.
• Lobular growth pattern, with tumor lobules separated by thin fibrous
connective tissue septa.
• Central areas of the lobules →greatest degree of maturation.
• Peripheral areas → immature cartilage & round or spindle shaped cells.
• Neoplastic cartilage may be replaced by bone in a manner similar to
normal endochondral ossification.
• Grade I chondrosarcomas closely mimic the appearance of a
chondroma, composed of chondroid matrix and chondroblasts
• Large, plump chondroblasts and binucleated chondrocytes seen.
• Calcification or ossification prominent, and mitoses are rare.
• Grade II chondrosarcomas show a greater proportion of
moderately sized nuclei and increased cellularity. More myxoid
with a less prominent hyaline matrix.
• Grade III chondrosarcomas are highly cellular and may show a
prominent spindle cell proliferation. Mitoses may be prominent .
Low-grade chondrosarcoma. The tumor cells
are larger than normal chondrocytes, with
larger, open-faced nuclei that have a uniform,
fine chromatin pattern. Several mitotic figures
are present, an uncommon finding in most
High-grade chondrosarcoma. Hypercellular
tumor contains pleomorphic cells, some with
large, bizarre nuclei. A few cells are spindle
infiltration between existing normal bone,
resulting in trabeculae that are closely
abutted and surrounded by tumor.
Mesenchymal chondrosarcoma. showing
sheets of small basophilic cells with
focal areas of cartilaginous
A, myxoid chondrosarcoma. Tumor cells are more closely arranged at the periphery of
the lobules. B, Radial, cordlike arrangement of tumor cells in myxoid chondrosarcoma.
Cells are embedded in grayish myxoid stroma
Treatment and Prognosis
• Prognosis in chondrosarcoma depends primarily on the
ability to adequately excise the tumor
• Radical surgical excision.
• Radiation and chemotherapy are less effective
• 5-year survival rate →43% to 95%
Primitive neuroectodermal tumor (PNET)
• Term used to describe a category of neoplasm of neuroectodermal origin
with variable cell differentiation.
• “small round cell tumors of childhood”
Divided into two categories
• Group (I) tumors→ pituitary adenomas and carcinoid tumors, represent
tumors that show predominantly epithelial differentiation.
• Group (II) tumors→ Olfactory neuroblastoma, Malignant melanoma,
Ewing’s sarcoma (EWS) display features that are predominantly
neural and non-epithelial in origin
• Ewing’s sarcoma is a sarcoma of the bone, classically
described under small round cell tumors.
• uncommonly involve the head and neck
• Incidence →1-3 cases per million of population per year.
• Skull tumors constitute about 2% of tumors.
• James Ewing (1866–1943) first described the tumor
• Balanced t(11:22) (q24;q12) chromosomal translocation- 85%
• EWS-FLI1 → central player in the pathogenesis of ES
• Overexpression of CD99
• Dysregulated signaling of receptor tyrosine kinase.
• Altered pathways of RB and p53
Some of the potential molecular targets of Ewing’s sarcoma described in this review
include: (a) EWS-FLI1 fusion protein, (b) its target genes, (c) growth factor receptor, cell-
surface receptors and (d) molecules involved in cell survival, proliferation and anti-
• Age: children and young adults, 5-25 years,
• Male: female= 2:1
• uncommon in blacks.
• Site: long bones of the extremities,
In head and neck region,
It involves skull, clavicle, maxilla and mandible.
Mandible ˃ maxilla.
• Earliest sign: Pain, usually of an intermittent nature, and
Swelling of the involved bone
• Facial neuralgia and lip paresthesia
• Jaw swelling
• Ulcerated intraoral mass
• Low -grade fever
• Elevated white blood cell count
• Extraskeletal form- Ewing’s Sarcoma of soft tissue.
• Extremely cellular neoplasm composed of solid sheets or masses
of small round cells with very little stroma.
• Cells are small and round, with scanty cytoplasm and relatively
large round or ovoid nuclei with dispersed chromatin and
• Cell borders are indistinct.
• Mitotic figures are common.
• Cells are positive for glycogen and are diastase resistant
• Geographic necrosis with perivascular sparing
many mitotic figures in the field
A, A lobular arrangement of primitive round cells with cytoplasmic clearing in
Ewing’s sarcoma/primitive neuroectodermal tumor. B, The cells of Ewing’s
sarcoma/primitive neuroectodermal tumor are usually uniform and small with
finely dispersed chromatin and small nucleoli.
Treatment and Prognosis
• Radiation therapy
• Five-year survival with a combination of surgery and
chemotherapy is 74%.
• Most common primary neoplasm of the skeletal system.
• Malignancy of plasma cells.
• Plasma cells are a subset of B-cells, which are the producers
of humoral immunity factors termed antibodies.
• Underlying pathology → Expansion of a single line of plasma
cells that replace normal bone marrow and produce
• Diffuse disease of the bone marrow.
• Frequent aberrations of chromosomes 1 and 14
• Other chromosomal abnormalities include 6q-, 7q-, 5q-
• Abnormal expression of the bcl-2 protein
• Mutations of the ras oncogene and p53 gene mutations
• Interleukin-6 (IL-6), considered the most important
myeloma growth factor
• Age: 60-65 years
• Sex: males> females
• More common among black people
• Site: mandible> maxilla
• Number of lytic foci or diffuse demineralization.
• Anemia, azotemia, hypercalcemia, recurrent infection.
• Extramedullary plasmacytoma- tonsils, nasopharynx, or
• Macroglobulinemia is a proliferation of plasmacytoid
lymphocytes secreting an IgM-protein.
• Patients often have lymphadenopathy and hepatosplenomegaly,
• Bony lesions are uncommon.
• Composed of sheets of closely packed cells resembling
plasma cells → round or ovoid cells with eccentrically
placed nuclei exhibiting chromatin clumping in a
‘cartwheel’ or ‘checkerboard’ pattern
• Two nuclei within a single cell membrane are seen
• Perinuclear halo may be present.
• Russell bodies are common
• Numerous mitochondria in a perinuclear distribution as
well as prominent Golgi complexes.
• Golgi complexes are most likely responsible for the
perinuclear halo which is observed by light microscopy.
• Hyperglobulinemia (monoclonal gammopathy)
• ↑ESR level
• Bence Jones protein in the urine → 60–85%
• Unusual protein which coagulates when the urine is heated to
40°–60° C and then disappears when the urine is boiled. It
reappears as urine is cooled.
Treatment and Prognosis.
• Bisphosphonate therapy → reduction of osteoclastic
activity and bone mineralization maintenance.
• Extramedullary plasmacytoma → radiation therapy
• Infection, anemia and kidney failure are the most
common immediate causes of death
• The possibility for the pathologist to correctly diagnose a bone
tumor depends to a large extent on the completeness of the
clinical and imaging information provided.
• Care of the patient requires a multidisciplinary approach
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